Abstract
Identification of T-cell epitopes from foreign proteins is the current focus of much research. Methods using simple two or three position motifs have proved useful in epitope prediction for major histocompatibility complex (MHC) class I, but to date not for MHC class II molecules. We utilized data from pool sequence analysis of peptides eluted from two HLA-DR13 alleles to construct a computer algorithm for predicting the probability that a given sequence will be naturally processed and presented on these alleles. We assessed the ability of this method to predict know self-peptides from these DR-13 alleles, DRB1 *1301 and *1302, as well as an immunodominant T-cell epitope. We also compared the predictions of this scoring procedure with the measured binding affinities of a panel of overlapping peptides from hepatitis B virus surface antigen. We concluded that this method may have wide application for the prediction of T-cell epitopes for both MHC class I and class II molecules.
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Apple, R. J., Erlich, H. A., Klitz, W., Manos, M. M., Becker, T. M., and Wheeler, C. M. HLA DR-DQ associations with cervical carcinoma show papillomavirus-type specifity. Nat Genet 6: 157–162, 1994
Brown, J. H., Jardetzky, T. S., Gorga, J. C., Stern, L. J., Urban, R. G. Strominger, J. L., and Wiley, D. C. Three-dimensional structure of the human class II histocompatibility antigen HLA-DR1. Nature 364: 33–39, 1993
Chen, W., Khilko, s., Fecondo, J., Margulies, D. H., and McCluskey, J. Determinant selection of major histocompatibility complex class I-restricted antigenic peptides is explained by class I-peptide affinity and is strongly influenced by nondominant anchor residues. J Exp Med 180: 1471–1483, 19994
Chicz, R. M., Urban, R. G., Lane, W. S., Gorga, J. C., Stern, L. J., Vignali, D. A. A., and Strominger, J. L. Predominant naturally processed peptides bound to HLA-DR1 are derived from MHC-related molecules and are heterogeneous in size. Nature 358: 764–768, 1992
Chicz, R. M., Urban, R. G., Gorga, J. C., Vignali, D. A. A., Lane, W. S., and Strominger, J. L. Specificity and promiscuity among naturally processed peptides bound to HLA-DR alleles. J Exp Med 178: 27–47, 1993
Davenport, M. P., Quinn, C. L., Chicz, R. M., Green, B. N., Willis, A. C., Lane, W. S., Bell, J. I., and Hill, A. V. S. Naturally processed peptides from two disease-resistance associate HLA-DR13 alleles show related sequence motifs and the effects of the dimorphism at position 86 of the HLA-DRβ chain. Proc Natl Sci USA 92: 6527–6571, 1995
Falk, K., Rötzachke, O., Stevanović, S., Jung, G., and Rammensee, H.-G. Allele-specific motifs revealed by sequencing of self-peptides eluted from MHC molecules. Nature 351: 290–296, 1991
Falk, K., Rötzschke, O., Stevanović, S., Jung, G., and Rammensee, H.-G. Pool sequencing of natural HLA-DR, DQ, and DP ligands reveals detailed peptide motifs, constraints of processing, and general rules. Immunogenetics 39: 230–242, 1994
Gorski, J., and Mach, B. Polymorphism of human Ia antigens: gene conversion betweens two DR loci results in new HLA-D/DR specificity. Nature 32: 67–70, 1986
Hammer, J., Takacs, B., and Sinigaglia, F. Identification of a motif for HLA-DR1 bindings peptides using M13 display libraries. J Exp Med 176: 1007–1013, 1992
Hammer, J., Belunis, C., Bolin, d., Papadopoulos, J., Walsky, R., Higelin, J., Danho, W., Sinigaglia, F., and Nagy, Z. A. High-affinity binding of short peptides to major histocompatibility complex class II molecules by short anchor combinations. Proc Natl Acad Sci USA 91: 4456–4460, 1994a
Hammer, J., Bono, E., Gallazzi, F., Belunis, C., Nagy, Z., and Sinigaglia, F. Precise prediction of major histocompatibility complex class II-peptide interaction based on peptide side chain scanning. J Exp Med 180: 2353–2358, 1994b
Hill, A. V. S., Allsopp, C. E. M., Kwiatkowski, d., Anstey, N. M., Twumasi, P., Rowe, P. A., Bennet, 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., aiddo, 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
Kubo, R. T., Sette, a., Grey, H. M., Appella, E., Sakaguchi, K., Zhu, N.-Z., Arnott, D., Sherman, N., Shabanowitz, J., Michel, H., Bodnar, W. M., Davis, T. A., and Hunt, d. F. Definition of specific peptide motifs for four major HLA-A alleles. J Immunol 152: 3913–1924, 1994
O'Sullivan, D., Arrhenius, T., Sidney, J., DelGuercio, M.-F., Albertson, M., Wall, M., Oseroff, C., Southwood, S., Colon, S. M., Gaeta, F. C.A., and Sette, A. On the interaction of promiscous antigenic peptides with different DR alleles. J Immunol 147: 2663–2669, 1991
Pamer, E. G., Harty, J. T., and Bevan, M. J. Precise prediction of a dominant class I MHC-restricted epitope of Listeria monocytogenes. Nature 353: 852–855, 1991
Reay, P. A., Kantor, R. M., and Davis, M. M. Use of global amino acid replacements to define the requirements for MHC binding and T cell recognition of moth cytochrome c (93–103). J Immuno 152: 3946–3957, 1994
Rothbard, J. B., and Taylor, W. R. A sequence pattern common to T cell epitopes. EMBO 7: 93–100, 1988
Rudensky, A. Y., Preston-Hurlburt, P., Hong, S.-C., Barlow, A., and Janeway, C. A. Sequence analysiss of peptides bound to MHC class II molecules. Nature 353: 622–627, 1991
Sette, A., Southwood, S., O'Sullivan, d., Gaeta, F. C. A., Sidney, J., and Grey, H. M. Effect of pH on MHC class II-peptide interactions. J Immunol 148: 844–851, 1992
Stern, L. J., Brown, J. H., Jardetzky, T. S., Gorga, J. C., Urban, R. G., Strominger, J. L., and Wiley, D. C. Crystal structure of the human class II MHC protein HLA-DR1 complexed with an influenza virus peptide. Nature 368: 215–221, 1994
Thursz, M. R., Kwiatkowski, D., Allsopp, C. E. M., Greenwood, B. M., Thomas, H. C., and Hill, A. V. S. Association Between an HLA class II allele and clearance of hepatitis B virus in The Gambia. N Engl J Med 332: 1065–1069, 1995
Tiercy, M.-M., Gorski, J., Betuel, H., Friedel, A. C., Gebuhrer, L., Jeanner, M., and Mach, B. DNA typing of DRw6 subtypes: correlation with DRB1 and DRB3 allelic sequences by hybridisation with oligonucleotide probes. Hum Immunol 24: 1–14, 1989
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Davenport, M.P., Ho Shon, I.A.P. & Hill, A.V.S. An empirical method for the prediction of T-cell epitopes. Immunogenetics 42, 392–397 (1995). https://doi.org/10.1007/BF00179401
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DOI: https://doi.org/10.1007/BF00179401