| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
/CD8 Interaction on the Surface of T Cells
Department of Immunology, Mayo Graduate and Medical Schools, Mayo Clinic, Rochester, MN 55905
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
is brought into close proximity with CD8 upon TCR/CD8
association. These interactions are not dependent on the
phosphorylation events characteristic of T cell activation. Thus, MHC
class I molecules, by binding to both CD8 and the TCR, mediate the
reorganization of T cell membrane components to promote cellular
activation. |
Introduction |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
and CD8. Simultaneous binding of soluble CD8 and TCR to the same MHC molecule in vitro has been shown by surface plasmon resonance studies. One group reported an enhanced affinity of the TCR for soluble class I molecules upon binding of the class I molecules to soluble CD8 (5). While this reported change in binding affinity might be taken as evidence of simultaneous binding of CD8 and the TCR to the same class I molecule, a second report argued that no such affinity changes could be seen under similar conditions (6). However, pertinent to the present discussion, in both studies the binding of soluble class I-CD8 complexes to surface-bound TCR could be inferred from the observed changes in plasmon resonance, indicating that it is sterically possible for class I molecules to be bound simultaneously by TCR and CD8.
Although binding of both CD8 and TCR to the same class I molecule has
not been directly demonstrated on the surface of living T cells,
several indirect methods have suggested that monomeric class I binding
and triggering of T cells requires the presence of CD8. Using
photoaffinity labeling, Luescher et al. (7) demonstrated
that labeling of a class I-restricted CTL clone with a soluble class I
monomer could be inhibited by mAbs to either CD8 or the CD8-binding
3 domain of class I. Additionally, Delon et al. (8)
showed that Ca2+ signaling induced by soluble
class I monomers was dependent on intact interactions between CD8 and
class I. Both of these findings support the hypothesis that CD8 and the
TCR bind simultaneously to class I molecules.
Several groups have demonstrated cell surface interactions between
members of the TCR/CD3 complex and the coreceptors CD4 and CD8 on
murine T cells and clones. Immunoprecipitation studies have revealed
that the majority of CD3 
-chains and a minority of TCR
-chains and
CD3
-, -, and 
-chains associate with CD4 or CD8 on resting T
cells (9, 10). However, there are conflicting reports
regarding which interactions between the coreceptors and TCR/CD3 are
affected during T cell activation. Osono et al. (11)
reported that upon activation with anti-TCR Abs, interactions
between CD3-, -, and -chains and coreceptor molecules remain
unchanged, whereas CD3-CD4/8 association is augmented during
activation. In contrast to this, Anel et al. (12) showed
enhanced CD3-CD8 association upon Con A activation. Of note, Thome
et al. (13) showed enhanced TCR-CD8 association upon
activation in a human T cell line. This association is dependent on the
activity of the tyrosine kinase Lck.
Fluorescence resonance energy transfer (FRET)2 is a property of fluorochromes readily adaptable to the study of proximity between molecules. When certain fluorochromes are brought into close proximity (<80 Å), they interact such that a fluorochrome that has been excited (the donor) can transfer energy to a second fluorochrome (the acceptor), causing it to fluoresce (14). Detection of enhanced acceptor fluorescence when only the donor has been directly excited indicates that the donor and acceptor fluorochromes are very close to one another. Although several groups have studied molecular interactions on cell surfaces using FRET (15, 16, 17, 18), here we employ novel combinations of commonly available fluorescent markers to assess interactions between T cell surface proteins.
|
Materials and Methods |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
2C TCR transgenic mice were originally described by D. Loh
(19) and have been maintained at the Mayo Clinic
(Rochester, MN). OT-1 TCR transgenic mice
(C57BL/6-TgN(TcrOva)1100 Mjb) were obtained from The Jackson Laboratory
(Bar Harbor, ME). All experiments were performed in compliance with
institutional and National Institutes of Health guidelines for animal
care and use.
Monomers and tetramers
Kb/SIYR and Kb/OVA
monomers and tetramers were prepared as previously described
(20). The expression vector for the production of
Kb tetramers and monomers was generated by
site-directed mutagenesis of Kb cDNA and cloned
into pET23 (Novagen, Madison, WI) for expression of protein in
Escherichia coli. The human
2-microglobulin construct was described
previously (21). SIYR (SIYRYYGL) and OVA (SIINFEKL)
peptides were generated at the Mayo Protein Core Facility.
PP1 treatment
Cells were incubated in 20 µM PP1 (22) (Biomol, Plymouth Meeting, PA) at 37°C for 30 min and stained on ice in the presence of 20 µM PP1.
Flow cytometry
The mAbs anti-CD8-allophycocyanin (53.6.7),
anti-CD4-allophycocyanin (RM4-5), anti-V2-PE (B20.1),
and anti-CD3-PE (145-2C11) were obtained from BD PharMingen (San
Diego, CA). CT-CD8a (anti-CD8) was purchased from Caltag
(Burlingame, CA). The anti-2C clonotypic mAb 1B2 (23)
was conjugated to PE using a Phycolink kit from Prozyme (San Leandro,
CA). Unconjugated polyclonal anti-IgG was obtained from ICN
Biomedicals (Costa Mesa, CA). FITC-conjugated anti-IgG was
purchased from Accurate Chemical and Scientific (Westbury, NY).
PE-conjugated anti-IgG was obtained from Serotec (Raleigh, NC).
Lymph node (LN) cells and thymocytes were isolated, and approximately
2 x 106 cells/sample were used. Cells were
incubated with 20 µg/ml Ab or tetramer or with 200 µg/ml monomer
for 20 min on ice. Reagents were diluted in HBSS containing 10 g/l BSA
and 0.2 g/l sodium azide. After incubation with Abs or tetramers, cells
were washed three times in HBSS/BSA/azide. Cells incubated with
monomers were fixed immediately after incubation. Paraformaldehyde was
added directly to the monomer-cell mixture. Cells were fixed in 2%
paraformaldehyde. FACS analyses were performed by the Mayo Flow
Cytometry Core Facility on a FACSCaliber (BD Biosciences, Franklin
Lakes, NJ), and data collected as log10
fluorescence were analyzed using CellQuest (BD Biosciences). FL3 (FRET)
signals were compensated by subtracting 28.8% of FL2 signal strength
to correct for bleed-over of signals from PE into FL3. An example of
the uncompensated and compensated mean fluorescence intensities
detected in FL2, FL3, and FL4 is shown for CD8+
cells stained with Kb/SIYR-PE,
anti-CD8-allophycocyanin, or both Kb/SIYR-PE
and anti-CD8-allophycocyanin (Table I
). Comparable FRET increases (gains in the FL3 channel) were detected
using compensated (115–4 = 111 arbitrary mean fluorescence
intensity units) or uncompensated (313–188 = 124 arbitrary mean
fluorescence intensity units) conditions.
|
Size exclusion gel filtration analysis was performed by the Mayo Protein Core Facility on a Superdex 200 10/30 column (Amersham Pharmacia Biotech, Piscataway, NJ) using a buffer flow rate of 0.5 ml/min. PBS was used as the buffer, and samples were run at room temperature. Samples of Kb/SIYR tetramer and monomer were diluted to 200 µg/ml in PBS, and 100 µl of each sample was injected into the column. The relative protein concentration was determined by measuring absorbance at 280 nm.
|
Results |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Allophycocyanin is a widely available phycobiliprotein that is
maximally excited by light of 615–655 nm (but not 488 nm), and emits
most efficiently at wavelengths above 650 nm (Fig. 1) (24). FITC and PE both absorb light efficiently at 488
nm, and fluoresce at wavelengths that overlap the excitation range for
allophycocyanin. The large size of phycobiliproteins and the existence
of multiple fluorescent moieties within each molecule make PE and
allophycocyanin unsuitable for precise measurements of distance using
FRET. However, quantitation of distances between fluorophores is not
necessary to effectively demonstrate that cell surface molecules are or
are not associating with one another. Thus, allophycocyanin paired with
either FITC or PE is an ideal set of reagents to study cell surface
interactions qualitatively by FRET. Using a standard two-laser flow
cytometry system, allophycocyanin fluorescence can be assessed both
when directly excited (aligned with the 635-nm laser) and when
indirectly excited by FRET (aligned with the 488-nm laser).
Allophycocyanin fluoresces in a range similar to that of the dyes PerCP
and Red613; thus, allophycocyanin fluorescence due to FRET can be
measured using standard detectors normally assigned to PerCP or Red613
(670 long-pass filter; Fig. 1, shaded regions). Importantly, neither
FITC nor PE fluoresces appreciably at wavelengths >670 nm (Fig. 1),
and any bleed-over present can be controlled by compensation.
|
). Furthermore, when fluorochromes were conjugated to reagents that were
not expected to interact, such as CD4 and class I-restricted TCRs, no
FRET was observed despite the presence of both fluorochromes on the
same cell (Fig. 4, b and d, dotted and bold
lines).
|
|
T cells that react against a particular peptide-MHC complex can be
effectively identified by their ability to bind to tetramers of soluble
MHC complexed with the reactive peptide (25). To
demonstrate that class I tetramers bind CD8 and recruit it to the TCR,
we stained LN cells from 2C and OT-1 TCR-transgenic mice (specific for
Kb/SIYR and Kb/OVA,
respectively) with 53.6.7-allophycocyanin (a CD8-specific mAb) and
PE-conjugated tetramers. With both 2C and OT-1
CD8+ cells, incubation with the relevant tetramer
stained the cells with PE and brought CD8 into close proximity with the
TCR, as evidenced by allophycocyanin fluorescence upon excitation at
488 nm (Fig. 3, shaded histograms). Tetramers containing an irrelevant peptide did not
label the CD8+ cells or induce FRET,
demonstrating that binding to the TCR is an essential step in the
recruitment of CD8. To show that recruitment of CD8 to the TCR is
dependent on the presence of MHC molecules, we stained LN cells with
1B2 or anti-V2, mAbs that recognize the 2C and OT-1 TCRs,
respectively (23, 26). PE-conjugated 1B2 and
anti-V2 bound effectively to their respective TCRs (Fig. 3, a and c), but were unable to recruit CD8 and
produced minimal FRET (Fig. 3, b and d). The
augmentation of the FRET signals produced by the interaction between
tetramers and anti-CD8 compared with those produced by anti-TCR
Abs and anti-CD8 implies that in the presence of tetramers, CD8 and
the TCR are colocalized and are not randomly distributed on the T cell
membrane. The inefficient induction of FRET by 1B2 and anti-V2
cannot be attributed to an intrinsic inability of these mAbs to
interact with anti-CD8-allophycocyanin, because FRET between these
reagents can be efficiently induced by artificial cross-linking with
polyclonal anti-IgG (data not shown). Therefore, the substantial
levels of FRET that occur upon tetramer binding are indicative of
tetramer-dependent association of CD8 and the TCR.
|
and do not inhibit one another from binding (data
not shown). To determine whether recruitment of CD8 to the TCR by MHC
class I tetramers is dependent on binding of CD8 by the MHC, we
incubated 2C and OT-1 LN cells with CT-CD8a and 53.6.7-allophycocyanin,
followed by relevant tetramer. As has been reported previously,
preincubation with CT-CD8a abrogated binding of
Kb/OVA to OT-1 CD8+ LN
cells, but only moderately reduced binding of
Kb/SIYR to 2C CD8+ cells
(23) (Fig. 3
, a and c). However,
blockade of the CD8-MHC interaction with CT-CD8a dramatically reduced
FRET acceptor fluorescence on 2C cells (Fig. 3b). This
indicates that CD8 recruitment to the TCR is dependent on MHC-CD8
binding. MHC class I-induced FRET is observed only with the CD8 coreceptor
To demonstrate that MHC class I-mediated recruitment of coreceptor
to the TCR is specific for CD8 and not CD4, we stained 2C and OT-1
thymocytes with PE-conjugated Kb/SIYR or
Kb/OVA tetramers as well as
allophycocyanin-conjugated anti-CD8 or anti-CD4 mAbs.
CD8+ thymocytes (mostly double-positive cells)
that were costained with 53.6.7-allophycocyanin and the relevant
tetramer produced an enhanced FRET acceptor signal. However,
CD4+ thymocytes (again, mostly double-positive
cells) labeled with relevant tetramer and anti-CD4-allophycocyanin
did not produce an acceptor signal despite the fact that the
CD4-labeled thymocytes bound relevant tetramer at approximately equal
levels with CD8-labeled thymocytes (Fig. 4). This difference in FRET signal despite similar levels of anti-CD4
and anti-CD8 implies that the association of tetramer with CD8 is
far greater than that expected due to random distribution of the TCR
and CD8.
TCR and CD8 receptors bind the same MHC ligand, assembling TCR/CD3/CD8 complexes
To this point, the experiments shown have used multivalent MHC
tetramers to assess TCR/CD8 interactions and have not addressed
directly the question of whether CD8 and TCR molecules bind to the same
class I molecule. To address this question, we stained 2C LN cells with
anti-CD3-PE and 53.6.7-allophycocyanin (anti-CD8), then
washed unbound Abs away. The stained 2C cells were then incubated with
unlabeled monomeric Kb/SIYR or
Kb/OVA. Immediately after incubation with
monomer, the cells were fixed with paraformaldehyde to preserve any
weak interactions between the class I monomers and the T cells. As
positive controls, we incubated stained cells with unlabeled
Kb/SIYR tetramers or anti-IgG polyclonal Abs,
reagents expected to efficiently assemble TCR/CD8 complexes. As a
negative control, the 2C cells were incubated with irrelevant
(Kb/OVA) tetramers or
monomers.Kb/SIYR tetramers and monomers, but
not Kb/OVA tetramers or monomers, induced
indirect allophycocyanin fluorescence on
CD3+8+ 2C T cells (Fig. 5, a and c). Since Kb/OVA
monomers were unable to induce FRET, we conclude that the FRET signal
is not due to weak nonspecific interactions that were inadvertently
preserved through immediate fixation. As before, preincubation with
CT-CD8a blocked Kb/SIYR-mediated FRET signaling
(Fig. 5, b and d). Maximal cross-linking of
anti-CD8 and anti-CD3 using anti-IgG induced
approximately the same intensity of FRET as
Kb/SIYR tetramers and monomers (Fig. 5e). FRET intensity is a function of both the efficiency of
formation of donor-acceptor complexes and the degree of proximity
between the complexed donor and acceptor fluorochromes. Thus, although
the absolute intensity of FRET observed using anti-CD3-PE as the
donor reagent (Fig. 5) is less than that induced by
Kb/SIYR-PE (Fig. 3b), we conclude that
the efficiency of TCR/CD3/CD8 complex formation is the same in both
cases, because monomer induced FRET is as efficient as tetramer- and
anti-IgG-induced FRET. To verify that our
Kb/SIYR preparation is indeed monomeric, we
recharacterized our preparation by analytical gel filtration. No
aggregates were detected in the monomeric preparation, while our
multimeric preparation of Kb/SIYR did contain
higher m.w. species as expected (Fig. 5g). Furthermore,
washing of stained cells incubated with monomers before fixation failed
to produce an augmented FRET signal (data not shown). Since tetramers
have sufficient avidity to remain bound during washing, it is implicit
that our preparation contains only low avidity monomers. Thus, a single
soluble MHC class I-peptide complex is able to bind to both CD8 and the
TCR, thereby recruiting CD8 to the TCR/CD3 complex.
|
Our experiments, which were conducted on ice and in an azide-containing
medium, imply that when the TCR is ligated by MHC, it associates with
CD8 in an ATP-independent fashion. To test formally whether Src family
kinase activity is required for MHC-induced TCR/CD8 interaction, we
preincubated 2C LN cells with the Src family kinase inhibitor PP1
before and during staining, then stained the cells with
anti-CD3-PE and 53.6.7-allophycocyanin, followed by monomeric
Kb/SIYR. The presence of PP1 at levels that
completely inhibit Src kinase activity in T and NK cells had no impact
upon the interaction between TCR and CD8 (Fig. 5f). This
demonstrates that CD8 can be recruited by MHC to the TCR complex
independent of cellular activation or phosphorylation of receptor
components.
|
Discussion |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Using FRET, we have directly demonstrated that CD8 and the TCR make
intimate contact on the surface of T cells upon binding to MHC class I
molecules. Soluble MHC-peptide monomers alone can induce this
association. Even though bivalent Abs were used to detect the relative
positions of CD3 and CD8, soluble monomeric class I molecules only
bind a single molecule each of TCR and CD8. This implies that the
interaction of CD8 with the TCR complex is the result of binding of CD8
and TCR molecules to the same MHC molecule.
Our experiments have shown FRET interactions between
allophycocyanin-labeled anti-CD8 mAbs and both PE-labeled tetramers
and PE-labeled anti-CD3 mAbs. The PE-tagged reagents are likely
to position their fluors at different distances from the cell membrane
and from the allophycocyanin-tagged anti-CD8 mAb. We do not know
the precise location of either the PE or allophycocyanin fluors on the
Abs or tetramers, nor do we know to what extent these fluors can move
about once the reagents are bound to cell surface molecules on T cells.
Thus, it is impossible to precisely state the relative positions of
TCR, CD3, and CD8 during class I ligation based on our data.
However, we can demonstrate that class I-dependent interactions occur
between the TCR and CD8 as well as between CD3 and CD8.
All our experiments used the anti-CD8 mAb 53.6.7 to detect
interactions between CD8 and CD3 or the TCR. We used this mAb
because other available Abs against CD8, such as CT-CD8a, block its
ability to bind to class I. However, it is possible that ligation of
CD8 with 53.6.7 might alter the ability of CD8 to interact with either
the TCR or class I. In fact, photoaffinity experiments show that
addition of 53.6.7 augments the ability of class I to bind to a
CD8+ T cell (7). However, in our
hands the presence of 53.6.7 only minimally affects the affinity of
tetramers for thymocytes (Fig. 4, a and c).
Furthermore, even in the absence of 53.6.7, Kb/OVA tetramers require
CD8 ligation to bind to OT-1 cells, while Kb/SIYR tetramer binding to
2C cells is augmented by intact CD8-class I interactions
(27). Thus, while 53.6.7 may affect the interaction of CD8
with class I or the TCR, it is unlikely that the observed class
I-dependent CD8-TCR interactions require the presence of 53.6.7.
Several reports indicate that a minor population of CD8 molecules on
resting T cells interacts with the TCR or members of the CD3 complex,
as evidenced by immunoprecipitation (9, 10). Although we
show that interactions between TCR and CD8 (Fig. 3) and between CD3
and CD8 (Fig. 5) are dramatically enhanced by class I ligation, our
results do not exclude a basal level of TCR/CD8 association. In fact,
while the anti-TCR reagents 1B2-PE and V2-PE did not produce
nearly as much FRET as did PE-conjugated tetramers, they did induce an
FL3 signal distinguishable from background (Fig. 3). This could be
interpreted as indicative of a low level interaction between the TCR
and CD8. In fact, while the dominant view in the literature is that CD8
is primarily not associated with the TCR until Ag ligation, some have
argued that the majority of coreceptor molecules on resting T cell are
associated with members of the CD3 complex (10). Under
this model, ligation of CD8 and the TCR by class I molecules would not
cause recruitment of CD8 to the TCR, but simply a rearrangement of the
TCR/CD3 complex, such that the orientations of the TCR and CD8 change
relative to one another. Our data do not exclude either model; however,
they show that class I ligation is capable of mediating such a
recruitment or rearrangement.
Since the interaction between the TCR and CD8 upon class I binding
occurs in cells poisoned with azide and in those with blocked kinase
function, no intracellular activation signals are required for this
association. CD8 and the TCR each associate with the same MHC molecule
based on their combined molecular avidity for class I, leading to the
assembly or rearrangement of the TCR/CD3/CD8 complex. As FRET was
observed between reagents targeting CD8 and CD3, it is evident that
complex assembly brings Lck into close proximity with CD3, one of
several members of the CD3 complex shown to be dependent on Lck for
phosphorylation. Recruitment of CD8-lck to CD3 would enhance
cellular activation by targeting CD3 for phosphorylation and
subsequent use as a docking molecule. Although we have demonstrated
CD8-TCR interactions that are class I dependent and Lck independent,
others have shown that cross-linking of CD3 in the absence of class I
is able to mediate the formation of complexes between the TCR and CD8
(13) or CD4 (18), and that these interactions
depend on the intact coupling of Lck to the relevant coreceptor. Our
findings do not exclude a model in which TCR/CD3 complexes interact
with CD4 or CD8 in the absence of MHC to modulate or propagate signals
emanating from the TCR. However, we do demonstrate that simultaneous
binding to class I is in itself sufficient to cause the intimate
association of CD8 with the TCR and CD3.
|
Footnotes |
|---|
2 Abbreviations used in this paper: FRET, fluorescence resonance energy transfer; LN, lymph node.
Received for publication November 27, 2000. Accepted for publication May 7, 2001.
|
References |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
3 domain of HLA-A2. Nature 345:41.[Medline]
bind peptide-MHC independently and with distinct kinetics. Immunity 10:219.[Medline]
chains with the accessory/co-receptor molecules CD4 and CD8 on nonactivated T lymphocytes. Eur. J. Immunol. 22:2475.[Medline]
complex. Eur. J. Immunol. 26:2093.[Medline]
T cell receptor. Proc. Natl. Acad. Sci. USA 96:1547., interferon, perforin, or costimulation through CD28. J. Virol. 73:3702. polypeptides and intracellular associations of CD8 with p56lck. Eur. J. Immunol. 28:745.[Medline]This article has been cited by other articles:
|
|
 |
|
  S. Radhakrishnan, L. N. Arneson, J. L. Upshaw, C. L. Howe, S. J. Felts, M. Colonna, P. J. Leibson, M. Rodriguez, and L. R. Pease TREM-2 Mediated Signaling Induces Antigen Uptake and Retention in Mature Myeloid Dendritic Cells J. Immunol., December 1, 2008; 181(11): 7863 - 7872. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. G. Schrum, D. Gil, E. P. Dopfer, D. L. Wiest, L. A. Turka, W. W. A. Schamel, and E. Palmer High-Sensitivity Detection and Quantitative Analysis of Native Protein-Protein Interactions and Multiprotein Complexes by Flow Cytometry Sci. Signal., June 5, 2007; 2007(389): pl2 - pl2. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Kao, M. A. Daniels, and S. C. Jameson Loss of CD8 and TCR binding to Class I MHC ligands following T cell activation Int. Immunol., December 1, 2005; 17(12): 1607 - 1617. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. O. Holman, E. R. Walsh, and S. C. Jameson Characterizing the Impact of CD8 Antibodies on Class I MHC Multimer Binding J. Immunol., April 1, 2005; 174(7): 3986 - 3991. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. K. Stanic, R. Shashidharamurthy, J. S. Bezbradica, N. Matsuki, Y. Yoshimura, S. Miyake, E. Y. Choi, T. D. Schell, L. Van Kaer, S. S. Tevethia, et al. Another View of T Cell Antigen Recognition: Cooperative Engagement of Glycolipid Antigens by Va14Ja18 Natural TCR J. Immunol., November 1, 2003; 171(9): 4539 - 4551. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.-A. Doucey, D. F. Legler, M. Faroudi, N. Boucheron, P. Baumgaertner, D. Naeher, M. Cebecauer, D. Hudrisier, C. Ruegg, E. Palmer, et al. The {beta}1 and {beta}3 Integrins Promote T Cell Receptor-mediated Cytotoxic T Lymphocyte Activation J. Biol. Chem., July 11, 2003; 278(29): 26983 - 26991. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Radhakrishnan, L. T. Nguyen, B. Ciric, D. R. Ure, B. Zhou, K. Tamada, H. Dong, S.-Y. Tseng, T. Shin, D. M. Pardoll, et al. Naturally Occurring Human IgM Antibody That Binds B7-DC and Potentiates T Cell Stimulation by Dendritic Cells J. Immunol., February 15, 2003; 170(4): 1830 - 1838. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-A. Doucey, L. Goffin, D. Naeher, O. Michielin, P. Baumgartner, P. Guillaume, E. Palmer, and I. F. Luescher CD3delta Establishes a Functional Link between the T Cell Receptor and CD8 J. Biol. Chem., January 24, 2003; 278(5): 3257 - 3264. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Buslepp, S. E. Kerry, D. Loftus, J. A. Frelinger, E. Appella, and E. J. Collins High Affinity Xenoreactive TCR:MHC Interaction Recruits CD8 in Absence of Binding to MHC J. Immunol., January 1, 2003; 170(1): 373 - 383. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Schott, N. Bertho, Q. Ge, M. M. Maurice, and H. L. Ploegh Class I negative CD8 T cells reveal the confounding role of peptide-transfer onto CD8 T cells stimulated with soluble H2-Kb molecules PNAS, October 15, 2002; 99(21): 13735 - 13740. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
