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*
Epimmune, San Diego, CA 92121;
National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; and
Wisconsin Regional Primate Research Center, University of Wisconsin, Madison, WI 53715
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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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Murine molecules, such as H-2Db, H-2Dd, and H-2Kb, frequently recognize anchor residues located in the middle of the peptide (6). This feature appears to be absent in human class I molecules. Both murine and human class I molecules also contain pockets that engage secondary anchor residues in the peptide, resulting in modulation of peptide binding affinity (6). Studies now suggest that a majority of human class I molecules can be classified in one of nine major supertypes, characterized by largely overlapping, but still distinct, peptide binding repertoires (16, 17, 18).
In contrast with this significant body of knowledge, little is known about the exact nature of the motifs recognized from other species including nonhuman primates. Recent studies indicate that human supertypes extend to chimpanzee (19) and that several, as yet unidentified, chimpanzee class I molecules are associated with a binding specificity resembling that of HLA-A2 or HLA-B7. By contrast, when the motif of the rhesus macaque class I molecule, Mamu-A*01, was defined (20), it was found to be characterized by the somewhat uncommon requirement for three anchor residues located at positions 2, 3, and the C terminus of the peptide, including an original specificity for proline at position 3. The feature of the three anchor residues located at positions 2, 3, and the C terminus has been noted in the case of HLA-A*01 (3), but apart from this isolated incidence, it is rather uncommon. This apparent difference between peptide binding of humans and macaques MHC class I is consistent with the extensive differences seen between human and rhesus macaque class I molecules (21).
The importance of defining nonhuman primate-associated motifs comes from the fact that nonhuman primate models of infectious diseases are important components of studies aimed at elucidating disease pathogenesis as well as useful elements for testing strategies aimed at development of specific vaccines and immunotherapies. Because of relatively abundant availability of animals, and of the close similarities of the immune systems and disease susceptibilities between macaques and humans, rhesus macaques represent one of the best models for the study of the immunobiology of a number of important diseases, including Lyme disease (22), hepatitis virus (23, 24), rotavirus (25), malaria (26, 27), and SIV (28, 29).
In particular, SIV infection of rhesus macaques serves as an excellent model to study the HIV infection and the immunologic responses to HIV in humans. Similar to HIV infection of humans, infection with SIV causes an AIDS-like disease in the majority of infected macaques (30). SIV and HIV are also similar in that both have tropism for CD4+ T cells (31, 32) and that structurally diverse HIV and SIV envelope glycoproteins use similar members of the chemokine receptor family as coreceptors (33, 34). Furthermore, HLA-A and -B locus homologues are found in rhesus macaques (21), and both human and macaque (Macaca mulatta) MHC class I (Mamu)3 molecules appear to bind gag and env epitopes from similar regions of both HIV and SIV (35). However, lack of exact knowledge of the molecular nature of epitopes bound by rhesus macaque MHC class I molecules has hindered studies in this field.
In the present study, we established quantitative peptide binding assays for four different rhesus macaque MHC class I molecules. Using these assays, we have defined specific peptide binding motifs associated with these different macaque MHC class I molecules. These results expand our knowledge of peptide-Mamu class I interactions and aid the development and testing of specific vaccine constructs.
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Materials and Methods |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Stable transfectants expressing rhesus macaque MHC class I molecules Mamu-A*11, Mamu-B*03, Mamu- B*04, and Mam-B*17 were generated by transferring each cloned cDNA into the HLA class I-deficient human B cell line 721.221 as previously described.4 Cells were grown in RPMI 1640 (Life Technologies, Rockville, MD) supplemented with 15% FBS (Gemini Bioproducts, Calabasa, CA), L-glutamine (Life Technologies), penicillin (100 IU/ml; Life Technologies), streptomycin (100 µg/ml; Life Technologies), and G418 (250 µg/ml; Life Technologies).
Peptides and 125I labeling
Peptides were obtained as lyophilized crude products from Chiron Technologies (San Diego, CA) or synthesized at Epimmune using standard t-Boc or F-moc solid-phase synthesis methods (36) and purified by standard HPLC methods. Peptides were stored in stock solutions at either 10 mg/ml or 20 mg/ml in 100% DMSO (Sigma, St. Louis, MO) and then diluted in RPMI 1640 for use in the cellular assays. HPLC-purified peptides were radiolabeled with 125I according to the chloramine-T method (37).
Live cell binding assays
Peptide binding to Mamu class I molecules was measured as previously described (4, 20). Briefly, Mamu class I-transfected 721.221 cells (106 cells/ml) were preincubated overnight at room temperature in RPMI 1640 supplemented with 15% FBS, L-glutamine, penicillin (100 IU/ml), and streptomycin (100 µg/ml). Cells were then washed twice in RPMI 1640 and resuspended to a final concentration of 1.25 x 107 cells/ml in RPMI 1640 supplemented with 3 µg/ml ß2-microglobulin (Scripps Clinic and Research Foundation, La Jolla, CA). Aliquots of 2 x 106 cells/well were incubated in 96-well U-bottom microtiter plates with 105 cpm (10 µl) of specific radiolabeled peptide (1–10 nM) and in the presence of a protease inhibitor mixture (final concentrations of 250 µg/ml PMSF (Sigma), 1.07 mg/ml EDTA (Sigma), 62.5 µg/ml pepstatin A (Sigma), 60 µg/ml TLCK (Calbiochem, La Jolla, CA), and 325 µg/ml phenanthroline (Sigma). Peptides representing CTL epitopes, or analogues thereof, were used as radiolabeled probes. Specifically, peptide GDYKLVEI was used for binding to Mamu-A*11, peptide RRHRILDMYL for binding to Mamu-B*03, peptide QGQYMNTPW for Mamu-B*04 binding, and peptide IRYPKTFGW for Mamu-B*17 binding (38). Following a 4-h incubation at 20°C, unbound peptide was removed by three washes in serum-free medium, followed by one passage through a FBS gradient. The amount of a bound labeled peptide was then determined by counting pelleted cells on a gamma scintillation counter.
For competitive inhibition assays, a dose range (0.001–100 nM) of unlabeled competitor peptide was coincubated with the radiolabeled probe and the cells. The concentration of peptide yielding 50% inhibition of the binding of the radiolabeled probe peptide (IC50) was then calculated.
Pocket analysis
On the basis of x-ray crystallographic studies of the structure of HLA class I molecules (14, 39, 40), residues 9, 45, 63, 66, 67, 70, and 99 were considered to make up the B pocket, and to determine the specificity for the residue in the second position of peptide ligands. Similarly, the polymorphic residues 77, 80, 81, and 116 were considered to determine the specificity of the F pocket for the C-terminal residue of peptide ligands. For pocket analyses, the residues comprising the B and F pockets of HLA alleles were compiled from the database published by Parham et al. (41). The sequences for Mamu-A*01 (42) and Mamu-B*03 (21) were also compiled from the published literature. The B and F pocket residues for Mamu-A*11, Mamu-B*04, and -B*17 were determined from DNA sequencing.4
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Results |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Previous studies using SIV-infected rhesus macaques had identified
SIV Nef- and Env-derived CTL epitopes restricted by the four macaque
class I alleles, Mamu-A*11, -B*03, -B*04, and -B*17 (38). These
epitopes were used to establish binding assays for the respective Mamu
molecules. Specifically, the Mamu-A*11-restricted CTL epitope Env
497–504 (GDYKLVEI), the Mamu-B*03-restricted epitope Nef 136–146
(ARRHRILDMYL), the Mamu-B*04-restricted epitope Nef 62–70 (QGQYMNTPW),
and an analogue of the Mamu-B*17-restricted epitope Nef 165–173
(IRFPKTFGW; F167
Y) were
125I-radiolabeled and tested for their capacity
to bind 721.221 cells transfected with the relevant rhesus macaque
class I alleles. Fig. 1
shows the results
of a representative experiment. Approximately 7% of the
Mamu-A*11-restricted epitope, Env 497, bound Mamu-A*11-expressing
cells. The specificity of interaction was demonstrated by the fact that
little or no binding to cells expressing either Mamu-B*03, -B*04, or
-B*17 was detected. Similarly, radiolabeled Nef 136, Nef 62, and Nef
165 (F167Y) peptides bound cells expressing
Mamu-B*03, -B*04, and -B*17, respectively. The percentage of bound
radiolabeled peptide ranged from 5 to 11.5%. In contrast, little or no
binding of peptides to cells expressing the irrelevant MHC restriction
was noted.
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). Typical inhibition curves are
shown for each of the radiolabeled peptides binding to its respective
MHC class I restriction element. Unlabeled peptide concentrations of
10–50 nM were sufficient to inhibit 50% of the binding of the
radiolabeled peptide, in good agreement with IC50
values reported for other molecules using live cell binding assays
(4, 20). In conclusion, the results presented herein
illustrate the establishment of sensitive binding assays, specific for
four different macaque class I molecules.
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The epitope length required for optimal binding to these macaque
class I molecules was analyzed next. Panels of truncated or extended
peptides were synthesized for each of the different epitopes and tested
for their ability to inhibit binding of the radiolabeled indicator
peptide to cells transfected with relevant macaque class I molecules
(Table I). In the case of the Mamu-A*11
molecule, the previously defined optimal 8-mer epitope, Env 497–504
(GDYKLVEI), and the LGDYKLVEI 9-mer epitope bound to
Mamu-A*11-expressing cells with IC50 values of 44
nM and 56 nM, respectively. Removal or addition of further residues at
either the C- or N-terminal ends resulted in decreases in binding
capacity of 10-fold or more as compared with the Env 497 epitope
(Table I).
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). These results are
compatible with a hydrophobic C-terminal residue (such as L or M),
being important for B*03 binding (see below), and peptides of 9–11
residues in length, being accommodated by B*03 molecules.
The best Mamu-B*04 binding capacity was detected in the case of Nef
62–70 (IC50 of 16 nM), previously mapped as the
optimal epitope recognized by Mamu-B*04-restricted CTL (Table I) (38).
Truncation of the N terminus by one residue yielded an 8-mer peptide
(QGQYMNTP) that was associated with a 2-fold reduction in binding
capacity (IC50 of 40 nM). Additional truncations
or extensions of either the C terminus or the N terminus resulted in
>50-fold decreases in binding capacity.
Finally, analysis of truncated and extended analogues of the Mamu-B*17
CTL epitope SIV Nef 165–173 (Table I) revealed that the known optimal
Mamu-B*17-restricted CTL epitope (IRFPKTFGW) was associated with the
best binding capacity (IC50 value of 22 nM).
Extended or truncated analogues at either the C terminus or the N
terminus were associated with decreased binding capacities ranging from
4.5-fold to 45-fold.
In conclusion, a good correlation exists between the results of CTL assays and peptide binding assays, thus emphasizing the biological relevance of the assays established and demonstrating that rhesus macaque class I molecules can accommodate ligands varying from 8 to 11 residues in length. Furthermore, these experiments identify optimal and biologically relevant epitopes that can be used to define specific binding motifs, as detailed below.
Definition of a Mamu-A*11-specific peptide binding motif
To define specific motifs, single substitution analogues of the relevant CTL epitopes were synthesized and tested in the appropriate binding assays. For each epitope, five to seven different substitutions were introduced at each position. The effect of conservative, semiconservative, and nonconservative substitutions was investigated. We arbitrarily defined main anchor positions as those associated with at least a 10-fold reduction in binding capacity for the majority of analogues tested. A position was defined as a secondary anchor position if at least a 3-fold reduction in binding was recorded for >50% of the substitutions tested.
The results of the analysis of single substitution analogues of the
Mamu-A*11 CTL epitope Env 497–504 (GDYKLVEI) are shown in Fig. 3A. Analogs with non- and
semiconservative substitutions at position 2 (P2) and P8 were
associated with significantly reduced binding capacities. At P2, the L,
K, or N substitutions for D resulted in 20- to 115-fold reductions in
binding. In contrast, a negatively charged E residue was well
accommodated, with a binding capacity or IC50 of
29 nM. Thus, a negatively charged residue (D or E) appeared to be
required at P2 for Mamu-A*11 binding.
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Although modest decreases in binding were noted at other positions (P3,
P5), no clear secondary anchor position was defined. In conclusion,
these data defined a Mamu-A*11 peptide binding motif based on the
presence of a negatively charged P2 residue and an aliphatic C terminus
(Table II).
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A Mamu-B*03 peptide motif was similarly determined by analyzing
the Mamu-B*03 binding of single substitution analogues of Nef 136–146
(Fig. 3B). All substitutions of the arginine at P2 (K, L, F,
N, or D) resulted in 15- to 20-fold reductions in binding capacity. All
substitutions for the C-terminal L were also associated with 10- to
15-fold decreases in binding capacity. This indicated P2 and the C
terminus as dominant anchor positions. Greater than 3-fold reductions
for a majority of the analogues were also observed at P1 and P5,
indicating that they may represent secondary anchor sites. In
conclusion, these data define a Mamu-B*03 motif based on a positive
charged arginine residue at P2 and an hydrophobic C terminus, with
possible secondary anchor roles for P1 and P5 (Table II).
Definition of a Mamu-B*04-specific peptide binding motif
The Mamu-B*04 binding capacity of a panel of Nef 62–70 analogues
was determined next (Fig. 3C). Six to seven single amino
acid substitutions were evaluated at each position. Most notably, all
substitutions for the G residue at P2 resulted in an almost complete
loss of binding capacity. Even the conservative A substitution resulted
in a >1500 binding reduction, indicating a strict requirement for G at
that position. A majority of the substitutions tested at P4 were
associated with >3-fold loss of activity (A, L, F, N, and D). In
particular, an N substitution resulted in a >10-fold decrease in
binding, and a D substitution decreased binding by >100-fold.
Significant effects were also noted at P5. Substitutions such as A, K,
and N resulted in 10- to 100-fold reductions in binding capacity, while
a D substitution affected binding >100-fold. Finally, >3-fold
decreases in binding capacity were also associated with a majority of
substitutions tested in P6. In conclusion, these results suggest a
crucial role for P2 and an important role also for P4, P5, and P6 in
Mamu-B*04 binding (Table II). A similar crucial role for a glycine
residue in P2 has previously been reported only in the case of the
murine MHC class I molecule Dd (7).
While no narrow affirmative requirement for the C terminus is evident,
there does seem to be an accommodation for an uncharged residue.
However, the Mamu-B*04 motif described herein is original in its lack
of strict dependence on a C-terminal anchor and the presence of three
contiguous secondary anchors in P4, P5, and P6.
Definition of a Mamu-B*17-specific peptide binding motif
Finally, a panel of Nef 165–173 analogues was tested for
Mamu-B*17 binding. This analysis revealed a crucial role for the W
residue at P9 (Fig. 3D). Three of the five substitutions
tested at the P9 C terminus resulted in >90-fold reductions in
binding. A conservative F substitution was well tolerated, while the
hydrophobic L substitution reduced binding capacity by 8-fold. No other
clear main anchor position was revealed by this analysis. However,
reductions in binding capacity of at least 3-fold were associated with
50% or greater of the substitutions made at P2, indicating its
possible role as a secondary anchor. In summary, these results indicate
that the presence of an aromatic residue at the P9 C terminus is the
main determinant of Mamu-B*17 binding capacity (Table II).
Pocket analysis of rhesus macaque class I alleles
Next, the P2 and C termini motif specificities, defined as
described above and summarized in Table II, were correlated with the
predicted structure of the B and F pockets of various rhesus macaque
class I molecules on the one hand and of human HLA class I molecules of
known motif specificities on the other hand.
In the case of the B pocket (Table III),
it was noted that class I molecules with preference for small residues,
such as Mamu-A*01, HLA-A*0101, and HLA-B*5801, are associated with the
consensus motif of M or T at residue 45, N at residue 66, and M at
residue 67 (16). In contrast, we found that other alleles,
associated with different known P2 specificities, such as Mamu-A*11,
HLA-B*4001, HLA-B*4402, Mamu-B*03, HLA-B*2705, and HLA-B*3901, are not
associated with the presence of this motif.
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). This motif is not found in any of the
other Mamu molecules that we have analyzed to date.
Finally, a B pocket consensus motif characterized by E at position 45
and small residues in position 67 (such as A or C) and a positive
charged residue in position 70 is apparently associated with a P2
specificity for positively charged residues, such as the one displayed
by HLA-B*27 and HLA-B*39 (43, 44, 45). We found that
Mamu-B*03, which has a similar P2 preference, specifically displays a
similar motif characterized by E, A, and H in P45, P67, and P70,
respectively (Table III).
In the case of the F pocket, alleles with preference for peptides with
positively charged C termini are associated with an F pocket motif of D
at positions 77 and 116, T at position 80, and L at position 81
(16). In particular, we hypothesized that the simultaneous
presence of the two negative charges, D at positions 77 and 116, is
crucial for high-affinity engagement of the positively charged C
termini (16). Such a motif is not found in either human
HLA alleles (16) or rhesus macaque class I alleles with a
preference for hydrophobic or aromatic residues at the C termini of
their ligands (Table IV).
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Overlap in peptide binding repertoire between rhesus macaque (Mamu) and human (HLA) class I molecules
Whether a significant overlap in peptide binding repertoire exists between HLA-B*4402 and Mamu-A*11 on one hand and HLA-B*2705 and Mamu-B*03 on the other hand was tested next. The human HLA molecule B*4402 is associated with a motif characterized by E at P2 and Y or F at the C terminus (46). This motif overlaps significantly with the motif defined in the current study for Mamu-A*11. Similarly, the reported motif of HLA B*2705, characterized by R at the P2 anchor and an aromatic/aliphatic C-terminal anchor (43, 44), overlaps significantly with the one herein defined for Mamu-B*03. As mentioned above, the analysis of polymorphic pockets of Mamu-A*11 and Mamu-B*03 also suggested that a significant overlap might exist in the peptide binding repertoire of these alleles with the human HLA-B*4402 and HLA-B*2705 class I molecules, respectively.
To test this hypothesis, a panel of peptides corresponding to
previously described HLA-B*4402 naturally occurring sequences of
bacterial or viral origin (46, 47, 48, 49, 50) were synthesized and
tested for their binding capacity to Mamu-A*11 (and Mamu-B*03 as a
specificity control). A total of five HLA-B*44 peptides were tested,
each a 9-mer peptide and each with the negatively charged E residue at
P2. Three peptides had aromatic residues at the C terminus, and two
peptides had L residues at the C terminus. Four of these five peptides
bound Mamu-A*11 with IC50 in the 100- to 500-nM
range. In contrast, none of these peptides bound appreciably to
Mamu-B*03 (Table V).
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). None
of these peptides bound appreciably to Mamu-A*11. In conclusion, the results presented in this section demonstrate a significant overlap in peptide binding specificity between specific rhesus macaque class I molecules and certain human HLA class I molecules of similar motif specificity.
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Discussion |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Our observations demonstrate that live cell binding assays can be used as a general method to measure peptide binding to rhesus macaque class I molecules. Additionally, the data provides a first glimpse at the relation between MHC binding affinity and immunogenicity in rhesus macaques. Previous data suggests that a binding affinity of 500 nM or less (and preferably 50 nM or less) is associated with immunogenicity in humans (51). The four SIV CTL epitopes tested here bind to their restricting macaque class I molecule with affinities <50 nM, suggesting that this correlation can also be extended to rhesus macaque class I molecules. As in the case with both human and murine class I, epitopes of 8–11 aa bind optimally to rhesus macaque class I molecules (6).
The present study defines four new rhesus macaque peptide binding motifs. Thus, together with the previously described Mamu-A*01 motif (20), a total of five macaque class I motifs have now been described. As discussed below, clarification of these motifs should greatly facilitate quantitation of immune responses and design of specific vaccine immunotherapies in the rhesus macaque.
The crucial features of the five macaque motifs thus far described can be analyzed in the context of the large body of information available for motifs of both murine and human origin. Several original features are apparent. First, most of the macaque motifs thus far defined do not strictly follow the P2/C-terminal main anchor paradigm that applies to most human class I motifs. For example, the Mamu-A*01 peptide motif did not possess strong P2 and C-terminal anchors, and its dominant anchor was found at P3 (20). Precedents for P3 anchors have been reported in the context of both the murine (H-2Dd) and human (HLA-A*01 and -B*08) systems (16, 52, 53).
Similarly, we show herein that Mamu-B*04 displays a strict requirement for G at P2 and lacks a defined requirement for the C terminus. A prominent influence on binding capacity is associated with the central portion of the peptide, with secondary anchor residues in P4, P5, and P6. This motif spacing is unique to rhesus class I molecules studied to date, although murine H-2Dd motif also requires a G at P2 (7). Conversely, the Mamu-B*17 motif does require an aromatic residue at the C terminus, but the P2 plays only a relatively minor and secondary role.
These original features of the macaque MHC class I peptide binding motifs are not unexpected given the relatively large sequence diversity and phylogenetic difference between human and rhesus macaque MHC class I molecules (21).
However, it was also noted that the Mamu-A*11 and -B*03 peptide binding motifs were strikingly similar to the HLA-B44 and -B27 motifs, respectively. These motif similarities were correlated with structural similarities in both B and F pocket structures of the relevant HLA-MHC class I molecules. The functional consequence of such structural similarities was demonstrated by the capacity of HLA-B44 ligands to specifically bind Mamu-A*11 and by the capacity of known endogenously bound HLA-B27 ligands to specifically bind to Mamu-B*03. As expected, this overlap in repertoire was only partial as previously seen in the case of HLA alleles belonging to the A3 or B7 supertypes (16). We do acknowledge the fact that the data regarding the HLA-B*4402 and -B*2705 ligand binding is generated by a different assay. However, the fact that the peptides used in the live cell binding assays were peptides isolated as naturally processed binding epitopes does to our mind suggest that this binding is biologically relevant by definition.
It should be noted that these four rhesus MHC class I peptide binding motifs can and will be further refined as more data points will be generated. Additionally, secondary effects might be revealed by the use of ligands with less optimal residues occupying the primary MHC class I pockets.
It is interesting to interpret these findings in the context of the recently described human HLA class I supertypes. A series of studies has demonstrated that the majority of human HLA class I can be classified in one of nine major supertypes (16, 17, 18). Recent data also demonstrates that HLA supertypes extend to the chimpanzee MHC class I molecules (19). Based on the results presented herein, it can be concluded that HLA supertypes similarly extend to rhesus macaques. The functional overlap in repertoires of many primate class I molecules could be reflective of a common ancestry of the class I genes encoding these molecules. Alternatively, convergent evolution could explain these structural and functional similarities. The results presented herein are also important because they enable future studies aimed at the identification of epitopes that would be recognized in the context of macaque MHC class I alleles.
Identification of macaque MHC class I-restricted peptide binding motifs will facilitate development of a variety of different rhesus macaque disease models, including Lyme disease (22), hepatitis virus (23, 24), rotavirus (25), and malaria (26, 27). Such advances could include the capacity to detect accurately and map specific immune responses, as a tool toward understanding disease course and ethiopathology (57), as well as enabling the design and testing of specific vaccine and immunotherapy strategies.
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Acknowledgments |
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Footnotes |
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2 Address correspondence and reprint requests to Dr. John L. Dzuris, Epimmune, 5820 Nancy Ridge Drive, San Diego, CA 92121. E-mail address:
3 Abbreviations used in this paper: Mamu, Macaca mulatta; P, position.
4 Evans, D. T., P. Jing, T. M. Allen, D. H. O’Conner, H. Horton, J. E. Venham, M. Piekarczyk, M. Dykhuzen, J. Mitchen, R. A. Rudersdorf, et al. 1999. Influence of MHC class I alleles on disease progression after AIDS virus infection. Submitted for publication.
Received for publication July 27, 1999. Accepted for publication October 13, 1999.
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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T. U. Vogel, T. C. Friedrich, D. H. O'Connor, W. Rehrauer, E. J. Dodds, H. Hickman, W. Hildebrand, J. Sidney, A. Sette, A. Hughes, et al. Escape in One of Two Cytotoxic T-Lymphocyte Epitopes Bound by a High-Frequency Major Histocompatibility Complex Class I Molecule, Mamu-A*02: a Paradigm for Virus Evolution and Persistence? J. Virol., October 11, 2002; 76(22): 11623 - 11636. [Abstract] [Full Text] [PDF]
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B. R. Mothe, J. Sidney, J. L. Dzuris, M. E. Liebl, S. Fuenger, D. I. Watkins, and A. Sette Characterization of the Peptide-Binding Specificity of Mamu-B*17 and Identification of Mamu-B*17-Restricted Epitopes Derived from Simian Immunodeficiency Virus Proteins J. Immunol., July 1, 2002; 169(1): 210 - 219. [Abstract] [Full Text] [PDF]
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J. L. Dzuris, J. Sidney, H. Horton, R. Correa, D. Carter, R. W. Chesnut, D. I. Watkins, and A. Sette Molecular Determinants of Peptide Binding to Two Common Rhesus Macaque Major Histocompatibility Complex Class II Molecules J. Virol., November 15, 2001; 75(22): 10958 - 10968. [Abstract] [Full Text] [PDF]
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T. M. Allen, B. R. Mothé, J. Sidney, P. Jing, J. L. Dzuris, M. E. Liebl, T. U. Vogel, D. H. O'Connor, X. Wang, M. C. Wussow, et al. CD8+ Lymphocytes from Simian Immunodeficiency Virus-Infected Rhesus Macaques Recognize 14 Different Epitopes Bound by the Major Histocompatibility Complex Class I Molecule Mamu-A*01: Implications for Vaccine Design and Testing J. Virol., January 15, 2001; 75(2): 738 - 749. [Abstract] [Full Text]
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J. Sidney, J. L. Dzuris, M. J. Newman, R. P. Johnson, K. Amitinder, C. M. Walker, E. Appella, B. Mothe, D. I. Watkins, and A. Sette Definition of the Mamu A*01 Peptide Binding Specificity: Application to the Identification of Wild-Type and Optimized Ligands from Simian Immunodeficiency Virus Regulatory Proteins J. Immunol., December 1, 2000; 165(11): 6387 - 6399. [Abstract] [Full Text] [PDF]
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D. T. Evans, P. Jing, T. M. Allen, D. H. O'Connor, H. Horton, J. E. Venham, M. Piekarczyk, J. Dzuris, M. Dykhuzen, J. Mitchen, et al. Definition of Five New Simian Immunodeficiency Virus Cytotoxic T-Lymphocyte Epitopes and Their Restricting Major Histocompatibility Complex Class I Molecules: Evidence for an Influence on Disease Progression J. Virol., August 15, 2000; 74(16): 7400 - 7410. [Abstract] [Full Text]
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