Abstract
Eight nonamer peptides that comply with the major anchor residue motifs (the combination of amino acid residues at positions 2 and 9), R-K and R-R, of HLA-B27 (B*2705)-binding peptides were synthesized and tested for their direct binding to HLA class I alpha chains by the HLA class I alpha chain refolding assay previously described. One was a known B27 (B*2705)-binding heat shock protein peptide, HSP89α (201–209), and the other seven were derived from the sequence of wild-type P53, a human tumor suppressor protein. A total of 36 HLA class I allospecificities were tested. HSP89α (201–209) and two P53 peptides, P53 (362–370) and P53 (378–386), all possessing the motif R-K, bound strongly to B27 (B*2705) alpha chains. A weak binding was seen for P53 (272–280) and P53 (334–342), both showing the motif R-R. Most of these B27-binding peptides were found to bind to A3 alpha chains as well. In addition, P53 (173–181) and P53 (334–342), both with the R-R motif, showed substantial binding with A31 alpha chains. All the peptides, carrying the motif R-K also showed weak binding with A31 alpha chains. The remaining two peptides, P53 (201–209) and P53 (282–290), with the motif R-R, did not show significant bininding with any of the alpha chains tested. This study demonstrates both the specificity of peptide binding to a given HLA allelic product and the occurence of cross-peptide-binding between the allelic products of different HLA loci.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bjorkman, P. J. and Parham, P. Structure, function, and diversity of class I major histocompatibility complex molecules. Annu Rev Biochem 59: 253–288, 1990
Breur-Vriesendorp, B. S., Dekker-Saeys, A. J., and Ivanyi, P. Distribution of HLA-B27 subtypes in patients with ankylosing spondilitis: the disease is associated with a common determinant of the various B27 molecules. Annu Rheum Dis 46: 353–356, 1987
Buxton, S. E., Benjamin, R. J., Clayberger, C., Parham, P., and Krensky, A. M. Anchoring pockets in human histocompatibility complex leukocyte antigen (HLA) class I molecules: analysis of the conserved B (“45”) pocket of HLA-B27. J Exp Med 175: 809–820, 1992
Carbone, F. R., Moore, M. W., Sheil, J. M., and Bevan, M. J. Induction of cytotoxic T lymphocytes by priming in vitro stimulation with peptides. J Exp Med 167: 1767–1779, 1988
Carreno, B., Koenig, S., Coligan, J. E., and Biddison, W. E. The peptide binding specificity of HLA class I molecules is largely alleli-specific and non-ovelapping. Mol Immunol 29: 1131–1140, 1992
Falk, K., Rotzschke, S., Stevanovic, 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
Garrett, T., Saper, M., Bjorkman, P., Strominger, J., and Wiley, D. Specificity pockets for the side chains of peptide antigens in HLA-Aw68. Nature 342: 692–696, 1989
Hunt, D. F., Henderson, R. A., Shabanowitz, J., Sagaguchi, K., Michel, H., Sevilir, N., Cox, A. L., Appela, 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 purifiied HLA-B27. Nature 353: 326–329, 1991
Lamb, P. and Crawford, L. Characterization of the human p53 gene. Mol Cell Biol 6: 1379–1385, 1986
Madden, D. R., Gorga, J. C., Strominger, J. L., and Wiley, D. C. The structure of HLA-B27 reveals nonamer self-peptides bound in an extended conformation. Nature 353: 321–325, 1991
Madden, D. R., Gorga, J. C., Strominger, J. L., and Wiley, D. C. The thr three-dimensional structure of HLA-B27 at 2.1 A resolution suggests a general mechanism for light peptide binding to MHC. Cell 70: 1035–1048, 1992
Milford, E. L., Kennedy, L. J., Yang, S. Y., Dupont, B., Lalouel, J.-M., and Yunis, E. J. Serological characterization of the reference panel of B-lymphoblastoid cell lines for factors of the HLA system. In B. Dupont (ed.): Immunobiology of HLA, vol. 1 Histocompatibility Testing 1987, pp. 19–38, Springer, New York, 1989
Richiardi, P. Serological cross-reactivity in the HLA system. In S. Ferrone, E. S. Curtoni, and S. Gorini (eds.): HLA antigens in clinical medicine and biology, pp. 93–97, Garland, New York, 1979
Richiardi, P., Cambon-Thomsen, A., and Menicucci, A. HLA-A, B, interlocus specificities. In E. D. Albert, M. P. Baur, and W. R. Mayr (eds): Histocompatibility Testing 1984, pp. 237–238, Springer, Berlin Heidelberg New York, 1984
Rotzschke, O., Falk, K., Stevanovic, S., Jung, G., and Rammansee, H.-G. Peptide motifs of closely related HLA class I molecules encompass substantial differences. Eur J Immunol 22: 2453–2456, 1992
Saper, M. A., Bjorkman, P. J., and Wiley, D. C. Refined structure of the human histocompatibility antigen HLA-A2 at 2.6 A resolution. J Mol Biol 219: 277–319, 1991
Tanigaki, N., Katagiri, M., Nakamuro, K., Kreiter, V. P., and Pressman, D. Common antigenic structures of HL-A antigens. II. Small fragments derived from papain-solubilized HL-A antigen molecules. Immunology 26: 155–168, 1974
Tanigaki, N., Fruci, D., Chersi, A., and Butler, R. H. Unfolded HLA class I alpha chains and their use in an assay of HLA class I-peptide binding. Hum Immunol, in press
Townsend, A. and Bodmer, H. Antigen presentation by class I-restricted T lymphocytes. Annu Rev Immunol 7: 601–624, 1989
Author information
Authors and Affiliations
Additional information
Correspondence to: N. Tanigaki.
Rights and permissions
About this article
Cite this article
Fruci, D., Rovero, P., Butler, R.H. et al. HLA class I binding of synthetic nonamer peptides carrying major anchor residue motifs of HLA-B27 (B*2705)-binding peptides. Immunogenetics 38, 41–46 (1993). https://doi.org/10.1007/BF00216389
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00216389