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*
Molecular Immunology Group, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom; and
Clinical Research Center Institute for Cancer Studies, University of Birmingham, Birmingham, United Kingdom
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Abstract |
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 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
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Introduction |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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The existence of T cell responses to EBV latent cycle proteins has long been recognized from work on healthy virus carriers (4, 5). Indeed, their ease of experimental detection in T cell memory owes much to the availability of EBV-transformed lymphoblastoid cell lines, expressing the full range of latent Ags, as a ready source of appropriate stimulator cells (1). Limiting dilution analysis (LDA)3 suggests that the frequency of T cells specific for EBV latent Ags is of the order of 20–100/106 PBMC in healthy virus carriers (6). Furthermore, recent work makes it clear that similar latent Ag-specific reactivities are also detectable within the primary T cell response to EBV infection as seen in infectious mononucleosis (IM) patients (6).
T cell reactivities against the EBV lytic cycle proteins are much less
well characterized, to some extent because the virus lytic cycle is
more difficult to reproduce in vitro, and work in this area has lagged
behind parallel studies in 
- and ß-herpes viral systems (7, 8).
Recent studies have now identified CTL responses directed against EBV
immediate early and early lytic cycle proteins (9, 10, 11, 12, 13). The clearest
evidence has, in fact, come from IM patients undergoing primary EBV
infection, in whom lytic Ag-specific reactivities were detectable in
direct CTL assays using ex vivo effectors, and subsequent in vitro
cloning of these effectors allowed the identification of a number of
lytic cycle epitopes (10). In contrast, relatively little is known
about the importance of T cells specific for lytic cycle epitopes in
long term virus carriers. In this context, Bogedain et al. (7) first
demonstrated existence of CTL memory to an HLA-B8-restricted epitope,
RAKFKQLL, from the immediate early BZLF1 protein (9), and subsequently
Elliott et al. used LDA to show that T cells reactive with the
HLA-B8-restricted RAKFKQLL epitope are also present in long term virus
carriers at frequencies comparable to those of T cells reactive with
HLA-B8-restricted epitopes from EBV latent proteins (13).
However, recent work has suggested that LDA may underestimate T cell
frequency by as much as 100-fold (14), and novel methods of estimating
frequencies of Ag-specific T cells have been developed. These include
assays to detect IFN-
release from epitope-specific CD8+
T cells following peptide stimulation (15) and the use of tetrameric
MHC-peptide complexes to directly stain T cells of the appropriate
specificity (16). Results obtained using these techniques have led to a
re-evaluation of the nature of both primary and memory responses to
viruses (11, 14, 17; reviewed in Ref. 18). For instance, in IM
patients, the frequency of EBV Ag-specific cells, measured directly
using tetrameric MHC-peptide complexes, ranged from 2% to as high as
44% CD8+ T cells in some cases (11). These values fell
following clinical recovery from IM, although populations of both
latent Ag-specific and lytic Ag-specific cells were still directly
detectable, at frequencies of >1% CD8+ T cells,
postconvalescence up to 3 yr later. How long Ag-specific cells persist
at these high levels remains to be determined. More importantly, it is
not known how the situation post-IM compares to that in the majority of
EBV carriers who experience clinically silent primary infection, mainly
during childhood, and then carry the virus for life.
Here we have analyzed the frequency and specificity of EBV-reactive T
cells within PBMC of long term EBV carriers with no history of IM as
well as in two individuals who suffered IM 10 and 15 yr ago. We used
three different methods to analyze T cell frequency; LDA, ELISPOT
assays to detect IFN- release, and direct staining of Ag-specific T
cells with MHC-peptide tetrameric complexes. The work focuses on the
responses to two epitopes from EBV lytic proteins and compares these
with the responses to epitopes from EBV latent proteins.
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Materials and Methods |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Whole blood was taken from 13 healthy adult virus carriers who tested positive for serum IgG Abs against EBV. PBMC were isolated by Lymphoprep (Nycomed Pharma, Oslo, Norway) density gradient centrifugation. HLA typing was conducted using standard serological methods or by PCR (19). HLA-A and -B types were as follows: donor RO: A2, A3, B7, B60; donor CH: A1, B8; donor VN: A2, B44, B65; donor PA: A1, A3, B7, B8; donor LC: A2, A11, B13, B60; donor LU: A1, A2, B8, B51; donor CM: A2, A11, B8, B44; donor DM: A1, A11, B8, B57; donor JB: A1, B7, B8; donor AR: A1, B8, B57; donor DA: A2, A11, B7, B44; donor JS: A2, B27; and donor PB: A1, A11, B22, B37. Donors VN and RO reported a history of suffering IM 10 and 15 yr ago, respectively. The other donors had no history of IM, and in several cases were known to have been seropositive for at least 10 yr.
Peptides
Seven peptides representing MHC class I-restricted EBV epitopes
are listed in Table I
(9, 12, 20, 21, 22, 23).
These were all synthesized commercially by Genosys (The Woodlands, TX)
or Alta Bioscience (University of Birmingham, Birmingham, U.K.),
with the exception of RPPIFIRRL, which was synthesized on an automatic
peptide synthesizer (Zinsser Analytical, Maidenhead, U.K.) using
conventional F-moc chemistry. All peptides were analyzed for purity by
reverse phase HPLC.
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LDAs were conducted essentially as previously described (6).
Fresh PBMCs were plated out in a range of dilutions, from 2,000–40,000
cells/well in 96-well round-bottom plates (24 replicates/input number).
Peptide-pulsed (5 µM) autologous PBMC (104) and
mononuclear feeder cells (105) from pooled buffy coats
(Blood Transfusion Service, Bristol, U.K.) were also added to each
well, always irradiated before their use. The cultures were maintained
in medium supplemented with 10% Lymphocult-T (Biotest, Birmingham,
U.K.) and 25 U/ml rIL-2, and fresh medium was added every 3–4
days. Epitope-specific responder frequencies were assayed on day 14
against 51Cr-labeled peptide-pulsed and unpulsed targets
(B-lymphoblastoid cell line (LCL) for lytic cycle epitopes or T2
cells transfected with the relevant MHC class I molecule for latent
epitopes). Maximum and spontaneous releases were calculated for each
target series. Wells were scored as positive if specific lysis exceeded
10%. Frequency values were estimated at which 37% of the wells were
negative for epitope recognition, using the method of maximum
likelihood, fulfilling single hit kinetics by 
2
analysis.
ELISPOT assay for single cell IFN- release
This assay was performed as previously described (15) to detect
Ag-specific T cells in fresh PBMC. Ninety-six-well polyvinylidene
difluoride-backed plates (Millipore, Bedford, MA) were precoated with
15 µg/ml of an anti-IFN- mAb, 1-DIK (MABTECH, Stockholm,
Sweden). PBMC were added in duplicate wells at 2.5 x
105, 1.25 x 105, and 6.25 x
104 cells/well in the presence of 2 µM peptide. The
plates were incubated overnight at 37°C in 5% CO2. The
cells were discarded the following day, and the second biotinylated
anti-IFN- mAb, 7-B6-1 biotin (MABTECH), was added at 1 µg/ml
and left for 3 h at room temperature, followed by
streptavidin-conjugated alkaline phosphatase (MABTECH) for an
additional 2 h. Individual cytokine-producing cells were detected
as dark spots after a 30-min reaction with 5-bromo-4-chloro-3-indolyl
phosphate and nitro blue tetrazolium using an alkaline
phosphatase-conjugate substrate kit (Bio-Rad, Richmond, CA). The spots
were counted under a dissection microscope. The number of specific T
cell responders was calculated after subtracting negative control
values.
Synthesis of MHC/peptide tetrameric complexes
Soluble MHC-peptide tetramers were produced using a method similar to that described previously (16). Recombinant MHC class I heavy chain or ß2m protein was produced in Escherichia coli cells transformed with the relevant expression plasmids. Expression of the heavy chain was limited to the extracellular domain, and the C-terminus of this domain was modified by the addition of a substrate sequence for the biotinylating enzyme BirA. HLA-A2, HLA-A11, and HLA-B8 complexes were folded in vitro using 30 mg of heavy chain protein, 25 mg of ß2m, and 10 mg of GLCTLVAML (HLA-A2), IVTDFSVIK (HLA-A11), RAKFKQLL (HLA-B8), or FLRGRAYGL (HLA-B8) peptides, respectively. Protease inhibitors (2 µg/ml pepstatin, 2 µg/ml leupeptin, and 0.2 mM PMSF) were used to preserve the protein. The MHC complexes were biotinylated using purified recombinant BirA enzyme at a final concentration of 10 µM, with 0.5 mM biotin and 5 mM ATP. The reaction was incubated at room temperature for 16 h to achieve a biotinylation level of 80%. The biotinylated MHC-peptide complexes were purified by gel filtration chromatography (using buffer containing 20 mM Tris (pH 8.0) and 50 mM NaCl) and anion exchange chromatography (0–0.5 M NaCl gradient). Tetramers were made by mixing the biotinylated protein complex with streptavidin-phycoerythrin (Sigma, St. Louis, MO) at a molar ratio of 4:1.
Cell staining
Fresh PBMC (106) were incubated on ice for 30 min in PBS with 0.1% BSA and 0.1% sodium azide containing 0.5 mg/ml of phycoerythrin-labeled tetrameric complex and saturating amounts of an anti-CD8 mAb conjugated to Tricolor (Caltag, South San Francisco, CA). For phenotypic analysis, selected samples were additionally incubated with one of a panel of mAbs directly conjugated to FITC. This panel consisted of anti-CD25 (Dako, Carpenteria, CA), anti-CD28 (Immunotech, Marseille, France), anti-CD45RA (Immunotech), anti-CD45RO (Dako), anti-CD57 (Becton Dickinson, Mountain View, CA), anti-CD62L (PharMingen, San Diego, CA), and anti-HLA-DR (Dako). The stained cells were fixed in PBS containing 2.5% formaldehyde and 1% FCS. Samples were analyzed by FACS using CellQuest software (Becton Dickinson). Lymphocytes were gated by forward and side angle light scatter. In each experiment cells stained with anti-CD3 and anti-CD8 were used to identify the CD8high subset of T cells that expressed CD3 and the markers set to allow analysis of this subset.
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Results |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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We first used LDA to estimate the frequency of T cells reactive
with two immunodominant epitopes from the EBV lytic proteins BZLF1 and
BMLF1 in eight EBV-seropositive individuals with one or both of the
appropriate HLA restricting alleles (HLA-B8 and HLA-A2). T cells
reactive with these epitopes were detected in all eight donors studied.
The data are summarized in the relevant section of Table II. The frequency of T cells specific for
the HLA-B8-restricted BZLF1 epitope (RAKFKQLL) (9) ranged from
60–725/106 PBMC (donors CH, PA, CM and LU), while the
frequency of T cells specific for the HLA-A2-restricted BMLF1 epitope
(GLCTLVAML) (12) ranged from 10–380/106 PBMC (donors LU,
JS, VN, RO, and LC). For comparison we estimated the frequency of T
cells reactive with immunodominant epitopes from EBV latent Ags in six
of these eight donors and in two additional individuals (DM and PB).
This involved the HLA-B8-restricted epitope, FLRGRAYGL (20); the
HLA-B7-restricted epitope, RPPIFIRRL (22); and the HLA-A11-restricted
epitope, IVTDFSVIK (23). The frequency of T cells reactive with these
epitopes, as estimated by LDA, ranged from undetectable levels to
240/106 PBMC in our donors. The T cell response to another
HLA-A11-restricted epitope (AVFDRKSDAK) is often subdominant, and
consistent with this, we found low frequencies of T cells specific for
this epitope in the three HLA-A11-positive donors studied (CM, DM, and
PB).
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Quantitation of T cell responses by ELISPOT assay
The frequency of T cells reactive with these same lytic and latent
cycle epitopes was then analyzed by ELISPOT assays, now in an extended
range of 13 healthy EBV carriers. This work was conducted once
preliminary studies had confirmed the specificity of the assay as used
with each of the peptides. In particular, there were no false positive
results observed using EBV-immune donors who did not have the relevant
HLA-restricting allele for the epitope in question or from
EBV-seronegative (i.e., noninfected) individuals who did have relevant
HLA alleles (data not shown). As shown in Table II
, ELISPOT assays
using lytic epitopes indicated that the frequency of HLA-B8-restricted,
RAKFKQLL-reactive T cells ranged from 250-2500/106 PBMC,
and the frequency of HLA-A2-restricted, GLCTLVAML-reactive T cells
ranged from 15–710/106 PBMC. T cells reactive with
dominant and subdominant epitopes from the EBV latent proteins were
also detected at frequencies up to 1000/106 PBMC, with
responses to the HLA-A11-restricted epitope IVTDFSVIK being
particularly strong. Most importantly, we noted that estimates of T
cell frequency using ELISPOTS were higher than those obtained using
LDAs, although the relative hierarchy of responses in any one
individual was not altered.
Enumeration of Ag-specific T cells using MHC-peptide tetrameric complexes
We next analyzed the frequency of T cells specific for two lytic
cycle epitopes (RAKFKQLL and GLCTLVAML) and two latent epitopes
(FLRGRAYGL and IVTDFSVIK) using MHC-peptide tetrameric complexes.
Tetramer specificity was first confirmed by staining control samples.
Thus, as shown in Fig. 1, the
HLA-B8/RAKFKQLL tetramer stained an HLA-B8-restricted,
RAKFKQLL-specific T cell clone (Fig. 1a), but did not stain
an HLA-B8-restricted T cell clone specific for a different epitope
(FLRGRAYGL; Fig. 1b). Furthermore, the HLA-B8/RAKFKQLL
tetramer did not stain CD8+ T cells in peripheral blood
taken from HLA-B8-negative EBV seropositive individuals (Fig. 1c) or from HLA-B8-positive, EBV-seronegative individuals
(Fig. 1d). The HLA-A2/GLCTLVAML, HLA-A11/IVTDFSVIK, and
HLA-B8/FLRGRAYGL tetramers were also tested in the same way, and their
specificity was confirmed (data not shown).
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and Fig. 2). Thus, using the HLA-B8/RAKFKQLL
tetramer, epitope-specific T cells were detected in all six
HLA-B8-positive individuals tested, and their frequencies were
unusually high. Fig. 2, a and b, show staining of
PBMC from donor CM in whom 6200/106 PBMC (4.3%
CD8+ T cells) reacted with the HLA-B8/RAKFKQLL tetramer and
from donor JB in whom 7,000/106 PBMC (5.0%
CD8+ T cells) reacted with this tetramer. A third
HLA-B8-positive donor, DM, gave 11,400 reactive cells/106
PBMC with this reagent, equivalent to 5.5% CD8+ T cells
(data not shown). The frequency of HLA-A2/GLCTLVAML-reactive T cells
was also high. Fig. 2, c and d, shows staining of
PBMC from donors LC and JS in whom 920/106 PBMC (0.4%
CD8+ T cells) and 2900/106 PBMC (0.8%
CD8+ T cells), respectively, reacted with the
HLA-A2/GLCTLVAML tetramer.
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, e and f,
show staining of PBMC from donors AR and JB in whom
2100/106 PBMC (0.7% CD8+ T cells) and
2900/106 PBMC (2.0% CD8+ T cells),
respectively, reacted with the HLA-B8/FLRGRAYGL tetramer. The frequency
of T cells reactive with the HLA-A11/IVTDFSVIK tetrameric complex
ranged from 1800–5000/106 PBMC (0.7–3.8%
CD8+ T cells; staining not shown).
In all but one of the 12 donors analyzed (the exception being PA), we
detected greater numbers of peptide-specific T cells by tetramer
staining than by the ELISPOT technique or LDA (Table II). Once again,
however, the hierarchy of responses to different epitopes within a
given individual remained consistent.
Phenotypic analysis of EBV-specific CTL within peripheral blood from long term virus carriers
Identification of EBV-specific memory T cells by
tetramer staining allowed us to analyze the expression of other surface
molecules on the same cells as markers of cell activation and
differentiation. FACS profiles from the phenotypic analysis of
HLA-B8/RAKFKQLL tetramer-reactive cells in donor DM are shown in Fig. 3, and the overall results obtained from
five individuals are summarized in Table III. CD25 (24), a marker of early T cell
activation, was not up-regulated on the tetramer-reactive cells,
whereas another activation marker, HLA-DR (25), was expressed at a high
level on a small proportion (up to 11%) of the cells. CD62L (26) tends
to be down-regulated on activated T cells, with expression being
regained in the stable memory state. Expression of this molecule was
variable, ranging from 8–72% of the Ag-specific T cells. CD45RO (27)
is thought to be a marker for activated and memory T cells. While it
was expressed on the majority (64–82%) of the tetramer population,
not all such cells were positive. Conversely, CD45RA, originally
thought to be a marker for Ag-inexperienced cells (27) was, in fact,
clearly present on some, albeit usually a minority, of the Ag-specific
cells. The tetramer-reactive cells were divided between the
CD28+ and CD28- T cell compartments. Finally,
CD57, which may be a marker for cells in a state of late or terminal
differentiation (28), was expressed on 69% of tetramer-reactive cells
in donor LC and was present on smaller proportions of tetramer-reactive
cells in the other donors.
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Discussion |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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We used three different methods to estimate the frequency of EBV
epitope-specific T cells in this cohort of individuals. We found that
the hierarchy of dominance of the different responses was similar
whatever the methodology, but the estimates of T cell frequency varied
substantially according to the method used. Lowest estimates were
obtained from LDAs (29); detection of T cells by this method depends on
their ability to proliferate in vitro and then to kill target cells in
cytotoxicity assays; given these constraints, LDAs could well
underestimate the frequency of Ag-specific T cells (30). By comparison,
higher estimates were obtained from ELISPOT assays. These assays detect
CD8+ T cells that secrete IFN- on short term in vitro
stimulation with the appropriate exact peptide Ag. Such cells are not
necessarily all cytotoxic, and conversely, not all Ag-specific T cells
will secrete IFN- upon peptide stimulation (31); Butz and Bevan
showed that these assays detect between 24–100% of T cells within a
clone, depending on the time during the restimulation cycle in which
the clone was tested (17). The highest estimates of frequencies were
obtained from direct staining with tetrameric complexes. This technique
depends only on expression of specific TCRs on the cell surface. Note,
however, that following stimulation with Ag, TCRs may be down-regulated
(32), and thus some acutely stimulated T cells may not be detected
using this method. Detection of EBV-specific T cells using tetrameric
complexes is not dependent on their function, and such T cells may not
all secrete IFN- upon stimulation or be cytolytic (31). Each of the
methods, therefore, has limitations. However, there was a good
correlation between results obtained from ELISPOT assays and those
obtained by direct staining with tetrameric complexes (Fig. 4a; r = 0.86,
p < 0.0001). On the average, epitope-specific T cell
frequencies were 4.4-fold higher when detected by the latter technique,
slightly above the 4-fold increase that might by inferred from in vitro
studies on cloned T cells (17). The correlation between results
obtained from ELISPOT assays and those obtained from LDAs was also good
(Fig. 4b; r = 0.88, p <
0.0001); ELISPOT values were, on the average, 5.3-fold higher than LDA
values. The correlation between LDA results and those obtained from
direct staining with tetrameric complexes was relatively poor (Fig. 4c; r = 0.69, p = 0.026).
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release and in vitro cloning assays. We analyzed T cell responses to two epitopes from EBV lytic cycle proteins BZLF1 and BMLF1 and found responses to these epitopes in all donors with the appropriate HLA type. We noted that T cells specific for the HLA-B8-restricted RAKFKQLL epitope from the lytic cycle protein BZLF1 could account for up to 5.5% of the circulating CD8+ population and outnumbered those specific for the HLA-B8-restricted FLRGRAYGL epitope from the EBV latent protein 3A. Hence, the unusual strength of the RAKFKQLL lytic epitope reactivity first noted during primary infection (10, 11) is maintained in T cell memory. T cells reactive with another epitope, GLCTLVAML, from the lytic protein BMLF1 were also easily detectable in the memory of HLA-A2-positive virus carriers. BZLF1 is the first immediate early protein to be expressed during the lytic replication cycle (34) and initiates expression of early genes, to which group BMLF1 belongs (35). BMLF1, in turn, functions as a trans-activator of other lytic cycle genes (36). T cell recognition of epitopes from these immediate early and early proteins should enable effective elimination of virus-producing cells at an early stage, perhaps before the formation and release of mature virions. Such T cells would, therefore, be expected to control foci of virus replication within the oropharynx (37) as well as regulate spontaneous reactivation from latency into lytic cycle within infected B cells generally (38, 39). The control of EBV lytic infection within B cells in peripheral blood may also have other advantages. EBV-transformed B cells that have been induced into lytic cycle have been shown to have superantigen-like activity in in vitro studies and stimulate T cells expressing the TCR Vß13 chains (40). Were this reproduced in vivo, persistent superantigenic stimulation of a major subset of T cells could be detrimental to the host. In addition, the lytic cycle gene BCRF1, expressed late in the lytic cycle, encodes an IL-10 homologue, and this might induce a general suppression of T cell responses (41).
T cells reactive with epitopes from EBV latent proteins were also easily detectable by tetramer staining in this cohort of individuals, with particularly strong responses to the HLA-A11-restricted IVTDFSVIK epitope in four of five donors studied. Interestingly, we were unable to detect a response to this epitope in the fifth donor, LC, who is Asian, consistent with previous reports of a mutation in this epitope in EBV isolates from South-East Asia (42). The magnitude of the latent Ag-specific response in long term virus carriers likewise reflects the fact that the immune system is continually being challenged by EBV-infected B cells that are reactivating in vivo from the resting state into virus-driven lymphoproliferation (38). This recrudescence of EBV-driven lymphoproliferative lesions and their control by EBV latent Ag-specific T cells appear to be central features of the healthy carrier state. Thus, when T cell control is ablated by immunosuppressive therapy, there is a significant incidence of lymphoproliferative disease, representing the opportunistic in vivo outgrowth of latently infected cells (43, 44, 45). Restoration of EBV latent Ag-specific responses with CTL preparations is, in fact, sufficient to reverse this otherwise fatal condition (44, 45). Therapies aimed at boosting T cell responses to EBV Ags may also be useful in the management of other EBV-associated malignancies, such as nasopharyngeal carcinomas and Hodgkin’s disease (46, 47, 48). The present methodologies, particularly ELISPOT and tetramer assays, open up the possibility of rapidly screening patients for their resident level of EBV-specific T cell immunity and also of monitoring the frequency of T cells with the appropriate specificities in in vitro reactivated populations destined for therapeutic use.
Perhaps the most important lesson to be learned from the present work, however, is the unexpectedly high proportion of circulating CD8+ T cells (up to 5.5%) that can persist in the blood of healthy individuals and be committed to a single viral epitope. It seems inherently unlikely that such numbers will be unique to the particular restriction elements studied here; to date, only a minority of the available EBV lytic cycle Ags (49) have been analyzed as potential targets for T cell responses, and so one can expect that epitopes from some of these as yet unexplored viral proteins will be equally immunodominant in the context of other HLA class I alleles. Hence, persistent infection with a genetically stable herpesvirus such as EBV can significantly influence the balance of reactivities within the circulating CD8+ T cell pool. This highlights the immunopathologies that might arise if the virus-induced response were to include reactivities either potentially cross-reactive with self Ags or cross-reactive with an allo-HLA Ag present on grafted tissue (50).
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Footnotes |
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2 Address correspondence and reprint requests to Dr. Margaret F. C. Callan, Molecular Immunology Group, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom OX3 9DS. E-mail:
3 Abbreviations used in this paper: LDA, limiting dilution analysis; IM, infectious mononucleosis; ELISPOT, enzyme-linked immunospot.
Received for publication July 27, 1998. Accepted for publication October 27, 1998.
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References |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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M. H. Fogg, D. Garry, A. Awad, F. Wang, and A. Kaur The BZLF1 Homolog of an Epstein-Barr-Related {gamma}-Herpesvirus Is a Frequent Target of the CTL Response in Persistently Infected Rhesus Macaques J. Immunol., March 15, 2006; 176(6): 3391 - 3401. [Abstract] [Full Text] [PDF]
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E. Landais, X. Saulquin, M. Bonneville, and E. Houssaint Long-Term MHC Class II Presentation of the EBV Lytic Protein BHRF1 by EBV Latently Infected B Cells following Capture of BHRF1 Antigen J. Immunol., December 15, 2005; 175(12): 7939 - 7946. [Abstract] [Full Text] [PDF]
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T. J. Scriba, M. Purbhoo, C. L. Day, N. Robinson, S. Fidler, J. Fox, J. N. Weber, P. Klenerman, A. K. Sewell, and R. E. Phillips Ultrasensitive Detection and Phenotyping of CD4+ T Cells with Optimized HLA Class II Tetramer Staining J. Immunol., November 15, 2005; 175(10): 6334 - 6343. [Abstract] [Full Text] [PDF]
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E. Amyes, A. J. McMichael, and M. F. C. Callan Human CD4+ T Cells Are Predominantly Distributed among Six Phenotypically and Functionally Distinct Subsets J. Immunol., November 1, 2005; 175(9): 5765 - 5773. [Abstract] [Full Text] [PDF]
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C. Mayr, D. M. Kofler, H. Buning, D. Bund, M. Hallek, and C.-M. Wendtner Transduction of CLL cells by CD40 ligand enhances an antigen-specific immune recognition by autologous T cells Blood, November 1, 2005; 106(9): 3223 - 3226. [Abstract] [Full Text] [PDF]
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G. M. Lauer, M. Lucas, J. Timm, K. Ouchi, A. Y. Kim, C. L. Day, J. S. zur Wiesch, G. Paranhos-Baccala, I. Sheridan, D. R. Casson, et al. Full-Breadth Analysis of CD8+ T-Cell Responses in Acute Hepatitis C Virus Infection and Early Therapy J. Virol., October 15, 2005; 79(20): 12979 - 12988. [Abstract] [Full Text] [PDF]
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N. H. Gudgeon, G. S. Taylor, H. M. Long, T. A. Haigh, and A. B. Rickinson Regression of Epstein-Barr Virus-Induced B-Cell Transformation In Vitro Involves Virus-Specific CD8+ T Cells as the Principal Effectors and a Novel CD4+ T-Cell Reactivity J. Virol., May 1, 2005; 79(9): 5477 - 5488. [Abstract] [Full Text] [PDF]
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H. M. Long, T. A. Haigh, N. H. Gudgeon, A. M. Leen, C.-W. Tsang, J. Brooks, E. Landais, E. Houssaint, S. P. Lee, A. B. Rickinson, et al. CD4+ T-Cell Responses to Epstein-Barr Virus (EBV) Latent-Cycle Antigens and the Recognition of EBV-Transformed Lymphoblastoid Cell Lines J. Virol., April 15, 2005; 79(8): 4896 - 4907. [Abstract] [Full Text] [PDF]
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C. Mayr, D. Bund, M. Schlee, A. Moosmann, D. M. Kofler, M. Hallek, and C.-M. Wendtner Fibromodulin as a novel tumor-associated antigen (TAA) in chronic lymphocytic leukemia (CLL), which allows expansion of specific CD8+ autologous T lymphocytes Blood, February 15, 2005; 105(4): 1566 - 1573. [Abstract] [Full Text] [PDF]
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K. F. May Jr, S. Roychowdhury, D. Bhatt, E. Kocak, X.-F. Bai, J.-Q. Liu, A. K. Ferketich, E. W. Martin Jr, M. A. Caligiuri, P. Zheng, et al. Anti-human CTLA-4 monoclonal antibody promotes T-cell expansion and immunity in a hu-PBL-SCID model: a new method for preclinical screening of costimulatory monoclonal antibodies Blood, February 1, 2005; 105(3): 1114 - 1120. [Abstract] [Full Text] [PDF]
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N. Khan, A. Hislop, N. Gudgeon, M. Cobbold, R. Khanna, L. Nayak, A. B. Rickinson, and P. A. H. Moss Herpesvirus-Specific CD8 T Cell Immunity in Old Age: Cytomegalovirus Impairs the Response to a Coresident EBV Infection J. Immunol., December 15, 2004; 173(12): 7481 - 7489. [Abstract] [Full Text] [PDF]
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V. Monsurro, E. Wang, Y. Yamano, S. A. Migueles, M. C. Panelli, K. Smith, D. Nagorsen, M. Connors, S. Jacobson, and F. M. Marincola Quiescent phenotype of tumor-specific CD8+ T cells following immunization Blood, October 1, 2004; 104(7): 1970 - 1978. [Abstract] [Full Text] [PDF]
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R. A. Du Pasquier, J. E. Schmitz, J. Jean-Jacques, Y. Zheng, J. Gordon, K. Khalili, N. L. Letvin, and I. J. Koralnik Detection of JC Virus-Specific Cytotoxic T Lymphocytes in Healthy Individuals J. Virol., September 15, 2004; 78(18): 10206 - 10210. [Abstract] [Full Text] [PDF]
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J.-M. Doisne, A. Urrutia, C. Lacabaratz-Porret, C. Goujard, L. Meyer, M.-L. Chaix, M. Sinet, and A. Venet CD8+ T Cells Specific for EBV, Cytomegalovirus, and Influenza Virus Are Activated during Primary HIV Infection J. Immunol., August 15, 2004; 173(4): 2410 - 2418. [Abstract] [Full Text] [PDF]
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S. P. Lee, J. M. Brooks, H. Al-Jarrah, W. A. Thomas, T. A. Haigh, G. S. Taylor, S. Humme, A. Schepers, W. Hammerschmidt, J. L. Yates, et al. CD8 T Cell Recognition of Endogenously Expressed Epstein-Barr Virus Nuclear Antigen 1 J. Exp. Med., May 17, 2004; 199(10): 1409 - 1420. [Abstract] [Full Text] [PDF]
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T. Shimizu, Y. Kozono, H. Kozono, M. Oda, and T. Azuma Affinity maturation of secreted IgM pentamers on B cells Int. Immunol., May 1, 2004; 16(5): 675 - 684. [Abstract] [Full Text] [PDF]
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 A. T.C. Chan, Q. Tao, K. D. Robertson, I. W. Flinn, R. B. Mann, B. Klencke, W. H. Kwan, T. W.-T. Leung, P. J. Johnson, and R. F. Ambinder Azacitidine Induces Demethylation of the Epstein-Barr Virus Genome in Tumors J. Clin. Oncol., April 15, 2004; 22(8): 1373 - 1381. [Abstract] [Full Text] [PDF]
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K. S. Voo, T. Fu, H. Y. Wang, J. Tellam, H. E. Heslop, M. K. Brenner, C. M. Rooney, and R.-F. Wang Evidence for the Presentation of Major Histocompatibility Complex Class I-restricted Epstein-Barr Virus Nuclear Antigen 1 Peptides to CD8+ T Lymphocytes J. Exp. Med., February 17, 2004; 199(4): 459 - 470. [Abstract] [Full Text] [PDF]
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E. Landais, X. Saulquin, E. Scotet, L. Trautmann, M.-A. Peyrat, J. L. Yates, W. W. Kwok, M. Bonneville, and E. Houssaint Direct killing of Epstein-Barr virus (EBV)-infected B cells by CD4 T cells directed against the EBV lytic protein BHRF1 Blood, February 15, 2004; 103(4): 1408 - 1416. [Abstract] [Full Text] [PDF]
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G. S. Taylor, T. A. Haigh, N. H. Gudgeon, R. J. Phelps, S. P. Lee, N. M. Steven, and A. B. Rickinson Dual Stimulation of Epstein-Barr Virus (EBV)-Specific CD4+- and CD8+-T-Cell Responses by a Chimeric Antigen Construct: Potential Therapeutic Vaccine for EBV-Positive Nasopharyngeal Carcinoma J. Virol., January 15, 2004; 78(2): 768 - 778. [Abstract] [Full Text] [PDF]
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I. Kang, T. Quan, H. Nolasco, S.-H. Park, M. S. Hong, J. Crouch, E. G. Pamer, J. G. Howe, and J. Craft Defective Control of Latent Epstein-Barr Virus Infection in Systemic Lupus Erythematosus J. Immunol., January 15, 2004; 172(2): 1287 - 1294. [Abstract] [Full Text] [PDF]
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L. I. Sakkas, G. Koussidis, E. Avgerinos, J. Gaughan, and C. D. Platsoucas Decreased Expression of the CD3{zeta} Chain in T Cells Infiltrating the Synovial Membrane of Patients with Osteoarthritis Clin. Vaccine Immunol., January 1, 2004; 11(1): 195 - 202. [Abstract] [Full Text] [PDF]
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K. Bickham, K. Goodman, C. Paludan, S. Nikiforow, M. L. Tsang, R. M. Steinman, and C. Munz Dendritic Cells Initiate Immune Control of Epstein-Barr Virus Transformation of B Lymphocytes In Vitro J. Exp. Med., December 1, 2003; 198(11): 1653 - 1663. [Abstract] [Full Text] [PDF]
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R. A. Du Pasquier, M. J. Kuroda, J. E. Schmitz, Y. Zheng, K. Martin, F. W. Peyerl, M. Lifton, D. Gorgone, P. Autissier, N. L. Letvin, et al. Low Frequency of Cytotoxic T Lymphocytes against the Novel HLA-A*0201-Restricted JC Virus Epitope VP1p36 in Patients with Proven or Possible Progressive Multifocal Leukoencephalopathy J. Virol., November 15, 2003; 77(22): 11918 - 11926. [Abstract] [Full Text] [PDF]
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R. S. Midgley, A. I. Bell, Q. Y. Yao, D. Croom-Carter, A. D. Hislop, B. M. Whitney, A. T. C. Chan, P. J. Johnson, and A. B. Rickinson HLA-A11-Restricted Epitope Polymorphism among Epstein-Barr Virus Strains in the Highly HLA-A11-Positive Chinese Population: Incidence and Immunogenicity of Variant Epitope Sequences J. Virol., November 1, 2003; 77(21): 11507 - 11516. [Abstract] [Full Text] [PDF]
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M. K. Gandhi, M. R. Wills, G. Okecha, E. K. Day, R. Hicks, R. E. Marcus, J. G. P. Sissons, and A. J. Carmichael Late diversification in the clonal composition of human cytomegalovirus-specific CD8+ T cells following allogeneic hemopoietic stem cell transplantation Blood, November 1, 2003; 102(9): 3427 - 3438. [Abstract] [Full Text] [PDF]
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A. L. Gervassi, P. Probst, W. E. Stamm, J. Marrazzo, K. H. Grabstein, and M. R. Alderson Functional Characterization of Class Ia- and Non-Class Ia-Restricted Chlamydia-Reactive CD8+ T Cell Responses in Humans J. Immunol., October 15, 2003; 171(8): 4278 - 4286. [Abstract] [Full Text] [PDF]
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E. Amyes, C. Hatton, D. Montamat-Sicotte, N. Gudgeon, A. B. Rickinson, A. J. McMichael, and M. F.C. Callan Characterization of the CD4+ T Cell Response to Epstein-Barr Virus during Primary and Persistent Infection J. Exp. Med., September 15, 2003; 198(6): 903 - 911. [Abstract] [Full Text] [PDF]
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M. W. J. Schreurs, K. B. J. Scholten, E. W. M. Kueter, J. J. Ruizendaal, C. J. L. M. Meijer, and E. Hooijberg In Vitro Generation and Life Span Extension of Human Papillomavirus Type 16-Specific, Healthy Donor-Derived CTL Clones J. Immunol., September 15, 2003; 171(6): 2912 - 2921. [Abstract] [Full Text] [PDF]
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D. Sauce, N. Rufer, P. Mercier, M. Bodinier, J.-P. Remy-Martin, A. Duperrier, C. Ferrand, P. Herve, P. Romero, F. Lang, et al. Retrovirus-mediated gene transfer in polyclonal T cells results in lower apoptosis and enhanced ex vivo cell expansion of CMV-reactive CD8 T cells as compared with EBV-reactive CD8 T cells Blood, August 15, 2003; 102(4): 1241 - 1248. [Abstract] [Full Text] [PDF]
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S. Chakrabarti, D. W. Milligan, D. Pillay, S. Mackinnon, K. Holder, N. Kaur, D. McDonald, C. D. Fegan, H. Waldmann, G. Hale, et al. Reconstitution of the Epstein-Barr virus-specific cytotoxic T-lymphocyte response following T-cell-depleted myeloablative and nonmyeloablative allogeneic stem cell transplantation Blood, August 1, 2003; 102(3): 839 - 842. [Abstract] [Full Text] [PDF]
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P. Meij, J. W. J. van Esser, H. G. M. Niesters, D. van Baarle, F. Miedema, N. Blake, A. B. Rickinson, I. Leiner, E. Pamer, B. Lowenberg, et al. Impaired recovery of Epstein-Barr virus (EBV)--specific CD8+ T lymphocytes after partially T-depleted allogeneic stem cell transplantation may identify patients at very high risk for progressive EBV reactivation and lymphoproliferative disease Blood, June 1, 2003; 101(11): 4290 - 4297. [Abstract] [Full Text] [PDF]
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L. Santodonato, G. D'Agostino, R. Nisini, S. Mariotti, D. M. Monque, M. Spada, L. Lattanzi, M. Paola Perrone, M. Andreotti, F. Belardelli, et al. Monocyte-Derived Dendritic Cells Generated After a Short-Term Culture with IFN-{alpha} and Granulocyte-Macrophage Colony-Stimulating Factor Stimulate a Potent Epstein-Barr Virus-Specific CD8+ T Cell Response J. Immunol., May 15, 2003; 170(10): 5195 - 5202. [Abstract] [Full Text] [PDF]
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N. Meidenbauer, J. Marienhagen, M. Laumer, S. Vogl, J. Heymann, R. Andreesen, and A. Mackensen Survival and Tumor Localization of Adoptively Transferred Melan-A-Specific T Cells in Melanoma Patients J. Immunol., February 15, 2003; 170(4): 2161 - 2169. [Abstract] [Full Text] [PDF]
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K. Kuzushima, N. Hayashi, A. Kudoh, Y. Akatsuka, K. Tsujimura, Y. Morishima, and T. Tsurumi Tetramer-assisted identification and characterization of epitopes recognized by HLA A*2402-restricted Epstein-Barr virus-specific CD8+ T cells Blood, February 15, 2003; 101(4): 1460 - 1468. [Abstract] [Full Text] [PDF]
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D. Sitki-Green, M. Covington, and N. Raab-Traub Compartmentalization and Transmission of Multiple Epstein-Barr Virus Strains in Asymptomatic Carriers J. Virol., February 1, 2003; 77(3): 1840 - 1847. [Abstract] [Full Text] [PDF]
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F. Buseyne, D. Scott-Algara, F. Porrot, B. Corre, N. Bellal, M. Burgard, C. Rouzioux, S. Blanche, and Y. Riviere Frequencies of Ex Vivo-Activated Human Immunodeficiency Virus Type 1-Specific Gamma-Interferon-Producing CD8+ T Cells in Infected Children Correlate Positively with Plasma Viral Load J. Virol., November 13, 2002; 76(24): 12414 - 12422. [Abstract] [Full Text] [PDF]
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T. U. Vogel, H. Horton, D. H. Fuller, D. K. Carter, K. Vielhuber, D. H. O'Connor, T. Shipley, J. Fuller, G. Sutter, V. Erfle, et al. Differences Between T Cell Epitopes Recognized After Immunization and After Infection J. Immunol., October 15, 2002; 169(8): 4511 - 4521. [Abstract] [Full Text] [PDF]
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P. Porcu, C. F. Eisenbeis, R. P. Pelletier, E. A. Davies, R. A. Baiocchi, S. Roychowdhury, S. Vourganti, G. J. Nuovo, W. L. Marsh, A. K. Ferketich, et al. Successful treatment of posttransplantation lymphoproliferative disorder (PTLD) following renal allografting is associated with sustained CD8+ T-cell restoration Blood, September 18, 2002; 100(7): 2341 - 2348. [Abstract] [Full Text] [PDF]
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H. Wedemeyer, X.-S. He, M. Nascimbeni, A. R. Davis, H. B. Greenberg, J. H. Hoofnagle, T. J. Liang, H. Alter, and B. Rehermann Impaired Effector Function of Hepatitis C Virus-Specific CD8+ T Cells in Chronic Hepatitis C Virus Infection J. Immunol., September 15, 2002; 169(6): 3447 - 3458. [Abstract] [Full Text] [PDF]
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H. L. Van Epps, M. Terajima, J. Mustonen, T. P. Arstila, E. A. Corey, A. Vaheri, and F. A. Ennis Long-lived Memory T Lymphocyte Responses After Hantavirus Infection J. Exp. Med., September 2, 2002; 196(5): 579 - 588. [Abstract] [Full Text] [PDF]
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N. Khan, N. Shariff, M. Cobbold, R. Bruton, J. A. Ainsworth, A. J. Sinclair, L. Nayak, and P. A. H. Moss Cytomegalovirus Seropositivity Drives the CD8 T Cell Repertoire Toward Greater Clonality in Healthy Elderly Individuals J. Immunol., August 15, 2002; 169(4): 1984 - 1992. [Abstract] [Full Text] [PDF]
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H. Tomiyama, T. Matsuda, and M. Takiguchi Differentiation of Human CD8+ T Cells from a Memory to Memory/Effector Phenotype J. Immunol., June 1, 2002; 168(11): 5538 - 5550. [Abstract] [Full Text] [PDF]
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Q. J. Wang, X.-L. Huang, G. Rappocciolo, F. J. Jenkins, W. H. Hildebrand, Z. Fan, E. K. Thomas, and C. R. Rinaldo Jr Identification of an HLA A*0201-restricted CD8+ T-cell epitope for the glycoprotein B homolog of human herpesvirus 8 Blood, May 1, 2002; 99(9): 3360 - 3366. [Abstract] [Full Text] [PDF]
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M. D. Catalina, J. L. Sullivan, R. M. Brody, and K. Luzuriaga Phenotypic and Functional Heterogeneity of EBV Epitope-Specific CD8+ T Cells J. Immunol., April 15, 2002; 168(8): 4184 - 4191. [Abstract] [Full Text] [PDF]
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M. P. Davenport, C. Fazou, A. J. McMichael, and M. F. C. Callan Clonal Selection, Clonal Senescence, and Clonal Succession: The Evolution of the T Cell Response to Infection with a Persistent Virus J. Immunol., April 1, 2002; 168(7): 3309 - 3317. [Abstract] [Full Text] [PDF]
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S. Kostense, K. Vandenberghe, J. Joling, D. Van Baarle, N. Nanlohy, E. Manting, and F. Miedema Persistent numbers of tetramer+ CD8+ T cells, but loss of interferon-gamma + HIV-specific T cells during progression to AIDS Blood, April 1, 2002; 99(7): 2505 - 2511. [Abstract] [Full Text] [PDF]
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F. Mattner, J.-K. Fleitmann, K. Lingnau, W. Schmidt, A. Egyed, J. Fritz, W. Zauner, B. Wittmann, I. Gorny, M. Berger, et al. Vaccination with Poly-L-Arginine As Immunostimulant for Peptide Vaccines: Induction of Potent and Long-Lasting T-Cell Responses against Cancer Antigens Cancer Res., March 1, 2002; 62(5): 1477 - 1480. [Abstract] [Full Text] [PDF]
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G. Koehne, K. M. Smith, T. L. Ferguson, R. Y. Williams, G. Heller, E. G. Pamer, B. Dupont, and R. J. O'Reilly Quantitation, selection, and functional characterization of Epstein-Barr virus-specific and alloreactive T cells detected by intracellular interferon-gamma production and growth of cytotoxic precursors Blood, March 1, 2002; 99(5): 1730 - 1740. [Abstract] [Full Text] [PDF]
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D. Sauce, M. Bodinier, M. Garin, B. Petracca, N. Tonnelier, A. Duperrier, J. V. Melo, J. F. Apperley, C. Ferrand, P. Herve, et al. Retrovirus-mediated gene transfer in primary T lymphocytes impairs their anti-Epstein-Barr virus potential through both culture-dependent and selection process-dependent mechanisms Blood, February 15, 2002; 99(4): 1165 - 1173. [Abstract] [Full Text] [PDF]
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T. U. Vogel, B. E. Beer, J. zur Megede, H.-G. Ihlenfeldt, G. Jung, S. Holzammer, D. I. Watkins, J. D. Altman, R. Kurth, and S. Norley Induction of anti-simian immunodeficiency virus cellular and humoral immune responses in rhesus macaques by peptide immunogens: correlation of CTL activity and reduction of cell-associated but not plasma virus load following challenge J. Gen. Virol., January 1, 2002; 83(1): 81 - 91. [Abstract] [Full Text] [PDF]
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K. Peggs, S. Verfuerth, A. Pizzey, J. Ainsworth, P. Moss, and S. Mackinnon Characterization of human cytomegalovirus peptide-specific CD8+ T-cell repertoire diversity following in vitro restimulation by antigen-pulsed dendritic cells Blood, January 1, 2002; 99(1): 213 - 223. [Abstract] [Full Text] [PDF]
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A. A. Pathan, K. A. Wilkinson, P. Klenerman, H. McShane, R. N. Davidson, G. Pasvol, A. V. S. Hill, and A. Lalvani Direct Ex Vivo Analysis of Antigen-Specific IFN-{gamma}-Secreting CD4 T Cells in Mycobacterium tuberculosis-Infected Individuals: Associations with Clinical Disease State and Effect of Treatment J. Immunol., November 1, 2001; 167(9): 5217 - 5225. [Abstract] [Full Text] [PDF]
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G. Gallot, R. Vivien, C. Ibisch, J. Lule, C. Davrinche, J. Gaschet, and H. Vie Purification of Ag-Specific T Lymphocytes After Direct Peripheral Blood Mononuclear Cell Stimulation Followed by CD25 Selection. I. Application to CD4+ or CD8+ Cytomegalovirus Phosphoprotein pp65 Epitope Determination J. Immunol., October 15, 2001; 167(8): 4196 - 4206. [Abstract] [Full Text] [PDF]
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M. D. Catalina, J. L. Sullivan, K. R. Bak, and K. Luzuriaga Differential Evolution and Stability of Epitope-Specific CD8+ T Cell Responses in EBV Infection J. Immunol., October 15, 2001; 167(8): 4450 - 4457. [Abstract] [Full Text] [PDF]
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W. Kuon, H.-G. Holzhutter, H. Appel, M. Grolms, S. Kollnberger, A. Traeder, P. Henklein, E. Weiss, A. Thiel, R. Lauster, et al. Identification of HLA-B27-Restricted Peptides from the Chlamydia trachomatis Proteome with Possible Relevance to HLA-B27-Associated Diseases J. Immunol., October 15, 2001; 167(8): 4738 - 4746. [Abstract] [Full Text] [PDF]
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A. Leen, P. Meij, I. Redchenko, J. Middeldorp, E. Bloemena, A. Rickinson, and N. Blake Differential Immunogenicity of Epstein-Barr Virus Latent-Cycle Proteins for Human CD4+ T-Helper 1 Responses J. Virol., September 15, 2001; 75(18): 8649 - 8659. [Abstract] [Full Text] [PDF]
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A. D. Hislop, N. H. Gudgeon, M. F. C. Callan, C. Fazou, H. Hasegawa, M. Salmon, and A. B. Rickinson EBV-Specific CD8+ T Cell Memory: Relationships Between Epitope Specificity, Cell Phenotype, and Immediate Effector Function J. Immunol., August 15, 2001; 167(4): 2019 - 2029. [Abstract] [Full Text] [PDF]
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A. L. N. Chapman, A. B. Rickinson, W. A. Thomas, R. F. Jarrett, J. Crocker, and S. P. Lee Epstein-Barr Virus-specific Cytotoxic T Lymphocyte Responses in the Blood and Tumor Site of Hodgkin's Disease Patients: Implications for a T-cell-based Therapy Cancer Res., August 1, 2001; 61(16): 6219 - 6226. [Abstract] [Full Text] [PDF]
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C. S. Gricks, E. Rawlings, L. Foroni, J. A. Madrigal, and P. L. Amlot Somatically Mutated Regions of Immunoglobulin on Human B-Cell Lymphomas Code for Peptides That Bind to Autologous Major Histocompatibility Complex Class I, Providing a Potential Target for Cytotoxic T Cells Cancer Res., July 1, 2001; 61(13): 5145 - 5152. [Abstract] [Full Text] [PDF]
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D. van Baarle, E. Hovenkamp, M. F. C. Callan, K. C. Wolthers, S. Kostense, L. C. Tan, H. G. M. Niesters, A. D. M. E. Osterhaus, A. J. McMichael, M. H. J. van Oers, et al. Dysfunctional Epstein-Barr virus (EBV)-specific CD8+ T lymphocytes and increased EBV load in HIV-1 infected individuals progressing to AIDS-related non-Hodgkin lymphoma Blood, July 1, 2001; 98(1): 146 - 155. [Abstract] [Full Text] [PDF]
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E. J. Novak, A. W. Liu, J. A. Gebe, B. A. Falk, G. T. Nepom, D. M. Koelle, and W. W. Kwok Tetramer-Guided Epitope Mapping: Rapid Identification and Characterization of Immunodominant CD4+ T Cell Epitopes from Complex Antigens J. Immunol., June 1, 2001; 166(11): 6665 - 6670. [Abstract] [Full Text] [PDF]
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T. M. Clay, A. C. Hobeika, P. J. Mosca, H. K. Lyerly, and M. A. Morse Assays for Monitoring Cellular Immune Responses to Active Immunotherapy of Cancer Clin. Cancer Res., May 1, 2001; 7(5): 1127 - 1135. [Abstract] [Full Text]
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V. Monsurro, M.-B. Nielsen, A. Perez-Diez, M. E. Dudley, E. Wang, S. A. Rosenberg, and F. M. Marincola Kinetics of TCR Use in Response to Repeated Epitope-Specific Immunization J. Immunol., May 1, 2001; 166(9): 5817 - 5825. [Abstract] [Full Text] [PDF]
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S. Nikiforow, K. Bottomly, and G. Miller CD4+ T-Cell Effectors Inhibit Epstein-Barr Virus-Induced B-Cell Proliferation J. Virol., April 15, 2001; 75(8): 3740 - 3752. [Abstract] [Full Text]
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Q. J. Wang, F. J. Jenkins, L. P. Jacobson, L. A. Kingsley, R. D. Day, Z.-W. Zhang, Y.-X. Meng, P. E. Pellet, K. G. Kousoulas, A. Baghian, et al. Primary human herpesvirus 8 infection generates a broadly specific CD8+ T-cell response to viral lytic cycle proteins Blood, April 15, 2001; 97(8): 2366 - 2373. [Abstract] [Full Text] [PDF]
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C. Rose, M. Green, S. Webber, D. Ellis, J. Reyes, and D. Rowe Pediatric Solid-Organ Transplant Recipients Carry Chronic Loads of Epstein-Barr Virus Exclusively in the Immunoglobulin D-Negative B-Cell Compartment J. Clin. Microbiol., April 1, 2001; 39(4): 1407 - 1415. [Abstract] [Full Text]
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K. Cwynarski, J. Ainsworth, M. Cobbold, S. Wagner, P. Mahendra, J. Apperley, J. Goldman, C. Craddock, and P. A. H. Moss Direct visualization of cytomegalovirus-specific T-cell reconstitution after allogeneic stem cell transplantation Blood, March 1, 2001; 97(5): 1232 - 1240. [Abstract] [Full Text] [PDF]
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P. J. R. Goulder, , M. M. Addo, M. A. Altfeld, E. S. Rosenberg, Y. Tang, U. Govender, N. Mngqundaniso, K. Annamalai, T. U. Vogel, M. Hammond, et al. Rapid Definition of Five Novel HLA-A*3002-Restricted Human Immunodeficiency Virus-Specific Cytotoxic T-Lymphocyte Epitopes by Elispot and Intracellular Cytokine Staining Assays J. Virol., February 1, 2001; 75(3): 1339 - 1347. [Abstract] [Full Text]
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P. J.R. Goulder, M. A. Altfeld, E. S. Rosenberg, T. Nguyen, Y. Tang, R. L. Eldridge, M. M. Addo, S. He, J. S. Muckerjee, M. N. Phillips, et al. Substantial Differences in Specificity of HIV-Specific Cytotoxic T Cells in Acute and Chronic HIV Infection J. Exp. Med., January 15, 2001; 193(2): 181 - 194. [Abstract] [Full Text] [PDF]
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T. O. Cameron, J. R. Cochran, B. Yassine-Diab, R.-P. Sekaly, and L. J. Stern Cutting Edge: Detection of Antigen-Specific CD4+ T Cells by HLA-DR1 Oligomers Is Dependent on the T Cell Activation State J. Immunol., January 15, 2001; 166(2): 741 - 745. [Abstract] [Full Text] [PDF]
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P. J.R. Goulder, Y. Tang, C. Brander, M. R. Betts, M. Altfeld, K. Annamalai, A. Trocha, S. He, E. S. Rosenberg, G. Ogg, et al. Functionally Inert HIV-Specific Cytotoxic T Lymphocytes Do Not Play a Major Role in Chronically Infected Adults and Children J. Exp. Med., December 18, 2000; 192(12): 1819 - 1832. [Abstract] [Full Text] [PDF]
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S. M. Smith, R. Brookes, M. R. Klein, A. S. Malin, P. T. Lukey, A. S. King, G. S. Ogg, A. V. S. Hill, and H. M. Dockrell Human CD8+ CTL Specific for the Mycobacterial Major Secreted Antigen 85A J. Immunol., December 15, 2000; 165(12): 7088 - 7095. [Abstract] [Full Text] [PDF]
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S.-K. Kim, L. Devine, M. Angevine, R. DeMars, and P. B. Kavathas Direct Detection and Magnetic Isolation of Chlamydia trachomatis Major Outer Membrane Protein-Specific CD8+ CTLs with HLA Class I Tetramers J. Immunol., December 15, 2000; 165(12): 7285 - 7292. [Abstract] [Full Text] [PDF]
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P. R. Dunbar, C. L. Smith, D. Chao, M. Salio, D. Shepherd, F. Mirza, M. Lipp, A. Lanzavecchia, F. Sallusto, A. Evans, et al. A Shift in the Phenotype of Melan-A-Specific CTL Identifies Melanoma Patients with an Active Tumor-Specific Immune Response J. Immunol., December 1, 2000; 165(11): 6644 - 6652. [Abstract] [Full Text] [PDF]
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M. K. Maini, N. Gudgeon, L. R. Wedderburn, A. B. Rickinson, and P. C. L. Beverley Clonal Expansions in Acute EBV Infection Are Detectable in the CD8 and not the CD4 Subset and Persist with a Variable CD45 Phenotype J. Immunol., November 15, 2000; 165(10): 5729 - 5737. [Abstract] [Full Text] [PDF]
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T. K. Hoffmann, K. Nakano, E. M. Elder, G. Dworacki, S. D. Finkelstein, E. Appella, T. L. Whiteside, and A. B. DeLeo Generation of T Cells Specific for the Wild-Type Sequence p53264-272 Peptide in Cancer Patients: Implications for Immunoselection of Epitope Loss Variants J. Immunol., November 15, 2000; 165(10): 5938 - 5944. [Abstract] [Full Text] [PDF]
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