Abstract
The chimpanzee (Pan troglodytes) is an important model for studying the immune response to several human pathogens, but the study of correlates of immunity has been hindered by the fact that little is known about the epitope-binding specificity of chimpanzee (Patr) class I MHC. In the present study we have characterized the peptide binding specificity of several common Patr class I molecules. Using single amino acid substitution analogs and large peptide libraries, quantitative peptide binding motifs have been derived for Patr A*0101, A*0701, A*0901, B*0101, and B*2401. Each molecule was found to bind peptides using position 2 and the C terminus as main anchor contacts. On the other hand, each Patr molecule is associated with a unique binding specificity, and the range of specificities is similar to that seen amongst HLA alleles. A high degree of cross-reactivity was noted between Patr A*0701 and Patr A*0901, suggesting the existence of a Patr-specific supertype. Consistent with previous studies suggesting that some cross-reactivity may exist between HLA and Patr alleles, Patr A*0901 was found to have an appreciable degree of cross-reactivity with molecules of the HLA A24-supertype. Finally, utilizing motif scans and peptide binding and intracellular cytokine staining assays, 77 hepatitis B virus (HBV)-derived epitopes were identified in five chimpanzees that were recently convalescent from acute HBV infection. Because the Patr alleles studied herein were found to be very common in two different chimpanzee populations, the present data should facilitate the use of chimpanzees for immunological studies.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bertoletti A, Ferrari C, Fiaccadori F, Penna A, Margolskee R, Schlicht HJ, Fowler P, Guilhot S, Chisari FV (1991) HLA class I-restricted human cytotoxic T cells recognize endogenously synthesized hepatitis B virus nucleocapsid antigen. Proc Natl Acad Sci USA 88:10445–10449
Bertoni R, Sidney J, Fowler P, Chesnut RW, Chisari FV, Sette A (1997) Human histocompatibility leukocyte antigen-binding supermotifs predict broadly cross-reactive cytotoxic T lymphocyte responses in patients with acute hepatitis. J Clin Invest 100:503–513
Bertoni R, Sette A, Sidney J, Guidotti LG, Shapiro M, Purcell R, Chisari FV (1998) Human class I supertypes and CTL repertoires extend to chimpanzees. J Immunol 161:4447–4455
Bui HH, Sidney J, Peters B, Sathiamurthy M, Sinichi A, Purton KA, Mothe BR, Chisari FV, Watkins DI, Sette A (2005) Automated generation and evaluation of specific MHC binding predictive tools: ARB matrix applications. Immunogenetics 57:304–314
Chang KM, Thimme R, Melpolder JJ, Oldach D, Pemberton J, Moorhead-Loudis J, McHutchison JG, Alter HJ, Chisari FV (2001) Differential CD4(+) and CD8(+) T-cell responsiveness in hepatitis C virus infection. Hepatology 33:267–276
Chisari FV, Ferrari C (1995) Hepatitis B virus immunopathogenesis. Annu Rev Immunol 13:29–60
Erickson AL, Kimura Y, Igarashi S, Eichelberger J, Houghton M, Sidney J, McKinney D, Sette A, Hughes AL, Walker CM (2001) The outcome of hepatitis C virus infection is predicted by escape mutations in epitopes targeted by cytotoxic T lymphocytes. Immunity 15:883–895
Guidotti LG, Matzke B, Schaller H, Chisari FV (1995) High-level hepatitis B virus replication in transgenic mice. J Virol 69:6158–6169
Gulukota K, Sidney J, Sette A, DeLisi C (1997) Two complementary methods for predicting peptides binding major histocompatibility complex molecules. J Mol Biol 267:1258–1267
Kondo A, Sidney J, Southwood S, del Guercio MF, Appella E, Sakamoto H, Celis E, Grey HM, Chesnut RW, Kubo RT et al (1995) Prominent roles of secondary anchor residues in peptide binding to HLA-A24 human class I molecules. J Immunol 155:4307–4312
Kondo A, Sidney J, Southwood S, del Guercio MF, Appella E, Sakamoto H, Grey HM, Celis E, Chesnut RW, Kubo RT, Sette A (1997) Two distinct HLA-A*0101-specific submotifs illustrate alternative peptide binding modes. Immunogenetics 45:249–258
Kowalski H, Erickson AL, Cooper S, Domena JD, Parham P, Walker CM (1996) Patr-A and B, the orthologues of HLA-A and B, present hepatitis C virus epitopes to CD8+ cytotoxic T cells from two chronically infected chimpanzees. J Exp Med 183:1761–1775
McKinney DM, Erickson AL, Walker CM, Thimme R, Chisari FV, Sidney J, Sette A (2000) Identification of five different Patr class I molecules that bind HLA supertype peptides and definition of their peptide binding motifs. J Immunol 165:4414–4422
Penna A, Chisari FV, Bertoletti A, Missale G, Fowler P, Giuberti T, Fiaccadori F, Ferrari C (1991) Cytotoxic T lymphocytes recognize an HLA-A2-restricted epitope within the hepatitis B virus nucleocapsid antigen. J Exp Med 174:1565–1570
Peters B, Tong W, Sidney J, Sette A, Weng Z (2003) Examining the independent binding assumption for binding of peptide epitopes to MHC-I molecules. Bioinformatics 19:1765–1772
Peters B, Bui HH, Sidney J, Weng Z, Loffredo JT, Watkins DI, Mothe BR, Sette A (2005) A computational resource for the prediction of peptide binding to Indian rhesus macaque MHC class I molecules. Vaccine 23:5212–5224
Rehermann B, Fowler P, Sidney J, Person J, Redeker A, Brown M, Moss B, Sette A, Chisari FV (1995) The cytotoxic T lymphocyte response to multiple hepatitis B virus polymerase epitopes during and after acute viral hepatitis. J Exp Med 181:1047–1058
Rehermann B, Lau D, Hoofnagle JH, Chisari FV (1996) Cytotoxic T lymphocyte responsiveness after resolution of chronic hepatitis B virus infection. J Clin Invest 97:1655–1665
Ruppert J, Sidney J, Celis E, Kubo RT, Grey HM, Sette A (1993) Prominent role of secondary anchor residues in peptide binding to HLA-A2.1 molecules. Cell 74:929–937
Sette A, Sidney J, Livingston B, Dzuris J, Crimi C, Walker CM, Southwood S, Collins EJ, Hughes A (2003) Class I molecules with similar peptide binding specificities are the result of both common ancestry and convergent evolution. Immunogenetics 54:830–841
Shimizu Y, DeMars R (1989) Production of human cells expressing individual transferred HLA-A,-B,-C genes using an HLA-A,-B,-C null human cell line. J Immunol 142:3320–3328
Sidney J, Grey HM, Southwood S, Celis E, Wentworth PA, del Guercio MF, Kubo RT, Chesnut RW, Sette A (1996a) Definition of an HLA-A3-like supermotif demonstrates the overlapping peptide-binding repertoires of common HLA molecules. Hum Immunol 45:79–93
Sidney J, Southwood S, del Guercio MF, Grey HM, Chesnut RW, Kubo RT, Sette A (1996b) Specificity and degeneracy in peptide binding to HLA-B7-like class I molecules. J Immunol 157:3480–3490
Sidney J, Southwood S, Oseroff C, Del Guercio MF, Sette A, Grey H (1998) Measurement of MHC/peptide interactions by gel filtration. Current protocols in immunology. Wiley, pp 18.3.1–18.3.19
Sidney J, Southwood S, Mann DL, Fernandez-Vina MA, Newman MJ, Sette A (2001) Majority of peptides binding HLA-A*0201 with high affinity crossreact with other A2-supertype molecules. Hum Immunol 62:1200–1216
Sidney J, Southwood S, Pasquetto V, Sette A (2003) Simultaneous prediction of binding capacity for multiple molecules of the HLA B44-supertype. J Immunol 171:5964–5974
Sidney J, Southwood S, Sette A (2005) Classification of A1- and A24-supertype molecules by analysis of their MHC–peptide binding repertoires. Immunogenetics 57:393–408
Southwood S, Sidney J, Kondo A, del Guercio MF, Appella E, Hoffman S, Kubo RT, Chesnut RW, Grey HM, Sette A (1998) Several common HLA-DR types share largely overlapping peptide binding repertoires. J Immunol 160:3363–3373
Thimme R, Wieland S, Steiger C, Ghrayeb J, Reimann KA, Purcell RH, Chisari FV (2003) CD8(+) T cells mediate viral clearance and disease pathogenesis during acute hepatitis B virus infection. J Virol 77:68–76
Acknowledgements
We would like to thank Fernando Buendia, Kris Haynes, and Fred Montoya for their expert technical assistance, and Dr. Howard M. Grey for helpful comments. The experiments described herein comply with the current laws of the United States of America. This work is supported by NIH National Institute of Allergy and Infectious Diseases contracts N01-AI-40023, N01-AI-40024, HHSN266200400006C, R01-AI20001 (FVC), R01-CA76403 (FVC), and a Skaggs training grant (S. Asabe).
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Below is the link to the Electronic supplementary material.
Rights and permissions
About this article
Cite this article
Sidney, J., Asabe, S., Peters, B. et al. Detailed characterization of the peptide binding specificity of five common Patr class I MHC molecules. Immunogenetics 58, 559–570 (2006). https://doi.org/10.1007/s00251-006-0131-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00251-006-0131-4