Abstract
Chimpanzees represent important models for studying several human pathogens. In the present study, we utilized a combinatorial peptide library to characterize the binding specificities of the chimpanzee class I molecules Patr A*0301 and A*0401, both of which are present in about 17% of chimpanzees. Patr A*0301 was found to recognize peptides using the canonical position 2/C-terminus spacing, with the small residues S, T, and A being the most preferred in position 2, and the positively charged residues R and K preferred at the C terminus. Patr A*0401 was found to recognize a more complex motif where the C terminus and then the residue in positions 1 and/or 5 are the primary anchors. Like A*0301, the C-terminal preference of A*0401 is for positively charged residues. At positions 1 and 5, positively charged and large residues are the most preferred, respectively. Coefficient values derived from the combinatorial library proved to be an efficient means for predicting A*0301 and A*0401 binders. The present data provide detailed information to facilitate the identification of potential T cell epitopes recognized in the context of two common chimpanzee class I alleles, and further validate the combinatorial library approach as an efficient method to characterize class I binding specificities.
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References
Adams EJ, Cooper S, Thomson G, Parham P (2000) Common chimpanzees have greater diversity than humans at two of the three highly polymorphic MHC class I genes. Immunogenetics 51:410–24
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
Cooper S, Erickson AL, Adams EJ, Kansopon J, Weiner AJ, Chien DY, Houghton M, Parham P, Walker CM (1999) Analysis of a successful immune response against hepatitis C virus. Immunity 10:439–449
de Groot NG, Otting N, Arguello R, Watkins DI, Doxiadis GG, Madrigal JA, Bontrop RE (2000) Major histocompatibility complex class I diversity in a West African chimpanzee population: implications for HIV research. Immunogenetics 51:398–409
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
Madden DR (1995) The three-dimensional structure of peptide-MHC complexes. Annu Rev Immunol 13:587–622
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
Moutaftsi M, Peters B, Pasquetto V, Tscharke DC, Sidney J, Bui HH, Grey H, Sette A (2006) A consensus epitope prediction approach identifies the breadth of murine T(CD8+)-cell responses to vaccinia virus. Nat Biotechnol 24:817–819
Nazif T, Bogyo M (2001) lobal analysis of proteasomal substrate specificity using positional-scanning libraries of covalent inhibitors. Proc Natl Acad Sci U S A 98:2967–2972
Peters B, Bui HH, Frankild S, Nielson M, Lundegaard C, Kostem E, Basch D, Lamberth K, Harndahl M, Fleri W, Wilson SS, Sidney J, Lund O, Buus S, Sette A (2006) A community resource benchmarking predictions of peptide binding to MHC-I molecules. PLoS Comput Biol 2:e65
Pinilla C, Appel JR, Blanc P, Houghten RA (1992) Rapid identification of high affinity peptide ligands using positional scanning synthetic peptide combinatorial libraries. Biotechniques 13:901–905
Pinilla C, Martin R, Gran B, Appel JR, Boggiano C, Wilson DB, Houghten RA (1999) Exploring immunological specificity using synthetic peptide combinatorial libraries. Curr Opin Immunol 11:193–202
Sidney J, Dzuris JL, Newman MJ, Johnson RP, Kaur A, Amitinder K, Walker CM, Appella E, Mothe B, Watkins DI, Sette A (2000) 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 165:6387–6399
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
Sidney J, Asabe S, Peters B, Purton KA, Chung J, Pencille TJ, Purcell R, Walker CM, Chisari FV, Sette A (2006) Detailed characterization of the peptide binding specificity of five common Patr class I MHC molecules. Immunogenetics 58:559–570
Stryhn A, Pedersen LO, Romme T, Holm CB, Holm A, Buus S (1996) Peptide binding specificity of major histocompatibility complex class I resolved into an array of apparently independent subspecificities: quantitation by peptide libraries and improved prediction of binding. Eur J Immunol 26:1911–1918
Udaka K, Wiesmuller KH, Kienle S, Jung G, Walden P (1995) Decrypting the structure of major histocompatibility complex class I-restricted cytotoxic T lymphocyte epitopes with complex peptide libraries. J Exp Med 181:2097–2108
Udaka K, Wiesmuller KH, Kienle S, Jung G, Tamamura H, Yamagishi H, Okumura K, Walden P, Suto T, Kawasaki T (2000) An automated prediction of MHC class I-binding peptides based on positional scanning with peptide libraries. Immunogenetics 51:816–828
Uebel S, Kraas W, Kienle S, Wiesmuller KH, Jung G, Tampe R (1997) Recognition principle of the TAP transporter disclosed by combinatorial peptide libraries. Proc Natl Acad Sci U S A 94:8976–8981
Acknowledgment
The experiments described herein comply with the current laws of the USA. This work is supported by NIH NIAID contracts N01-AI-40023 (AS), N01-AI-40024 (AS), HHSN266200400006C (AS), HHSN266200400080C/N01 AI40080 (CP), R01-AI20001 (FVC), R01-CA76403 (FVC), and a Skaggs Training Grant (SA).
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Sidney, J., Peters, B., Moore, C. et al. Characterization of the peptide-binding specificity of the chimpanzee class I alleles A*0301 and A*0401 using a combinatorial peptide library. Immunogenetics 59, 745–751 (2007). https://doi.org/10.1007/s00251-007-0243-5
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DOI: https://doi.org/10.1007/s00251-007-0243-5