Abstract
An evolutionary analysis of self peptides reported to be bound by HLA class I molecules showed that these peptides are largely derived from proteins that have been highly conserved in the history of mammals. These proteins also often have universal tissue expression and have a higher than average frequency of highly hydrophilic residues. The peptides themselves are generally still more highly conserved than the source proteins and have a higher frequency of highly hydrophobic residues, evidently often derived from conserved hydrophobic cores of the source proteins. These results suggest that the mechanism by which peptides are derived for MHC presentation may preferentially select peptides from conserved protein regions. In the case of parasite-derived peptides, such a mechanism would be adaptive in that it would reduce the likelihood of escape mutants.
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Auger, I. C. Computational techniques to predict amphipathichelical segments. In R. M. Epand, (ed.): The Amphipathic Helix, pp. 7–19, CRC Press, Boca Raton, 1993
Berke, G. The binding and lysis of target cells by cytotoxic lymphocytes: molecular and cellular aspects. Annu Rev Immunol 12: 735–773, 1994
DiBrino, M., Parker, K. C., Shiloach, J., Turner, R. V., Tsuchida, T., Garfield, M., Biddison, W. E., and Coligan, J. E. Endogenous peptides with distinct amino acid anchor residue motifs bind to HLA-A1 and HLA-B8. J Immunol 152: 620–631, 1994
Driscoll, J., Brown, M. G., Finley, D., and Monaco, J. J. MHC-linked LMP gene products specifically after peptidase activities of the proteasome. Nature 365: 262–264, 1993
Engelhard, V. H. Structure of peptides associated with class I MHC molecules. Curr Opin Immunol 6: 13–23, 1994
Engelhard, V. H., Appella, E., Benjamin, D. C., Bodnar, W. M., Cox, A. L., Chen, Y., Henderson, R. A., Huczko, E. L., Michel, H., Sakaguchi, K., Shabanowitz, J., Sevilir, N., Slingluff, C. L., and Hunt, D. F. Mass spectrometric analysis of peptides associated with the human class I MHC molecules HLA-A2 and HLA-B7 and identification of features that determine binding. Chem Immunol 57: 39–62, 1993
Fidock, D. A., Gras-Masse, H., Lepers, J.-P., Brahami, K., Benmohamed, L., Melloak, S., Guerin-Marchand, C., Londaro, A., Raharimalala, L., Meis, J. F. G. M., Langsley, G., Roussilhon, C., Tartar, A., and Druilhe, P. Plasmodium falciparum liver stage antigen-1 is well conserved and contains potent B and T cell determinants. J Immunol 154: 190–204, 1994
Gaczynska, M., Rock, K. L., and Goldberg, A. L. λ-interferons and expression of MHC genes regulate protein hydrolysis by proteasomes. Nature 365: 264–267, 1993
Germain, R. N. MHC-dependent antigen processing and peptide presentation: providing ligands for T lymphocyte activation. Cell 76: 287–299, 1994
Goldberg, A. L. and Rock, K. L. Proteolysis, proteasomes, and antigen presentation. Nature 357: 375–379, 1992
Guo, H.-C., Jardetzky, T. S., Garret, T. P. J., Lane, W. S., Strominger, J. L., and Wiley, D. C. Different length peptides bind to HLA-Aw68 similarly at their ends but bulge out in the middle. Nature 360: 364–367, 1992
Harris, P. E., Colovai, A., Lin, Z., Dalla Favera, R., and Sucia-Foca, N. Naturally processed HLA class I bound peptides from c-myc-transfected cells reveal allele-specific motifs. J Immunol 151: 5966–5974, 1993
Hill, A. V. S., Allsopp, C. E. M., Kwiatkowski, D., Anstey, N. M., Twumasi, P., Rowe, P. A., Bennett, S., Brewster, D., McMichael, A. J., and Greenwood, B. M. Common West African HLA antigens are associated with protection from severe malaria. Nature 352: 595–600, 1991
Hill, A. V. S., Elvin, J., Willis, A. C., Aidoo, M., Allsopp, C. E. M., Gotch, F. M., Gao, X. M., Takiguchi, M., Greenwood, B. M., Townsend, A. R. M., McMichael, A. J., and Whittle, H. C. Molecular analysis of the association of HLA-B53 and resistance to severe malaria. Nature 360: 434–439, 1992
Huczko, E. L., Bodnar, W. M., Benjamin, D., Sakaguchi, K., Zhu, N. Z., Shabanowitz, J., Henderson, R. A., Appells, E., Hunt, D. F., and Engelhard, V. H. Characteristics of endogenous peptides eluted from the class I MHC molecule HLA-B1 determined by mass spectrometry and computer modeling. J Immunol 151: 2572–2587, 1993
Hughes, A. L. and Nei, M. Evolution of the major histocompatibility complex: independent origin of nonclassical class I genes in different groups of mammals. Mol Biol Evol 6: 559–579, 1989
Hughes, A. L. and Nei, M. Evolutionary relationships of class II major-histocompatibility-complex genes in mammals. Mol Biol Evol 7: 491–514, 1990
Hunt, D. F. and Engelhard, V. H. HLA-A2.1 associated peptides from a mutant cell line: a second pathway of antigen presentation. Science 255: 1264–1266, 1992
Hunt, D. F., Henderson, R. A., Shabanowitz, J., Sakaguchi, K., Michel, H., Sevilir, N., Cox, A., Appella, E., and Engelhard, V. H. Characterization of peptides bound to the class I MHC molecule HLA-A2.1 by mass spectrometry. Science 255: 1261–1263, 1992
Jardetzky, T. S., Lane, W. S., Robinson, R. A., Madden, D. R., and Wiley, D. C. Identification of self peptides bound to purified HLA-B27. Nature 353: 326–329, 1991
Johnson, R. P., Tocha, A., Yang, L., Mazzara, G. P., Panicali, D. L., Buchanan, T. M., and Walker, B. D. HIV-1 gag-specific cytotoxic T lymphocytes recognize multiple highly conserved epitopes. J Immunol 147: 1512–1521, 1991
Kimura, M. The Neutral Theory of Molecular Evolution, Cambridge University, Press, Cambridge, 1983
Margalit, H., Sponge, J. L., Cornette, J. L., Cease, K. B., Delisi, C., and Berzofsky, J. A. Prediction of immunodominant helper T cell antigenic sites from the primary sequence. J Immunol 138: 2213–2229, 1987
Monaco, J. J. A molecular model of MHC class-I-restricted antigen processing. Immunol Today 13: 173–178, 1992
Neefjes, J. J., Momburg, F., and Hammerling, G. J. Selective and ATP-dependent translocation of peptides by the MHC-encoded transporters. Science 261: 769–771, 1993
Powis, S. J., Deverson, E. V., Coadwell, W. J., Cirnela, A., Huskisson, N. S., Smith, H., Butcher, G. W., and Howard, J. C. Effect of polymorphism of an MHC-linked transporter on the peptides assembled in a class I molecule. Nature 357: 211–215, 1992
Shepherd, J. C., Schumacher, T. N. M., Ashton-Rickardt, P. G., Imaeda, S., Ploegh, H. L., Janeway, C. A., Jr., and Tonegawa, S. TAP1-dependent peptide translocation in vitro is ATP dependent and peptide selective. Cell 74: 577–584, 1993
Townsend, A. R. M., Gocth, F. M., and Davey,J. Cytotoxic T cells recognize fragments of the influenza nucleoprotein. Cell 42: 417–467, 1985
Townsend, A., Ohlen, C., Bastin, J., Ljunggren, H. G., Foster, L., and Kavre, K. Association of class I major histocompatibility heavy and light chains induced by viral peptides. Nature 340: 443–448, 1989
Vriz, S., Taylor, M., and Mechali, M. Differential expression of two Xenopus c-myc proto-oncogenes during development. EMBO J 8: 4091–4097, 1989
Wyckoff, E., Natalie, D., Nolan, J. M., Lee, M., and Hsieh, T.-S. Structure of the Drosophila DNA topoisomerase II gene: nucleotide sequence and homology among topoisomerases II. J Mol Biol 205: 1–13, 1989
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Hughes, A.L., Hughes, M.K. Self peptides bound by HLA class I molecules are derived from highly conserved regions of a set of evolutionarily conserved proteins. Immunogenetics 41, 257–262 (1995). https://doi.org/10.1007/BF00172149
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DOI: https://doi.org/10.1007/BF00172149