Abstract
INTRACELLULAR binding of antigenic peptides by polymorphic class I major histocompatibility complex molecules creates the ligands recognized by receptors of CD8+ T cells1. Previously described in vitro assays of peptide binding to class I molecules have been limited by either the low proportion of accessible binding sites or the lack of allelic specificity2–6. Here we describe a system in which the human class I molecule HLA-B27 binds considerable amounts of an influenza peptide with precise allelic discrimination. Binding requires viable cells, is stimulated by γ-interferon and is inhibited by brefeldin A. Our results are consistent with the presence of fairly stable 'empty' HLA-B27 molecules at the cell surface. By contrast, analysis of the binding of a second influenza peptide indicates that empty HLA-Aw68 molecules are relatively short-lived. We speculate that HLA-B27 might bind extracellular peptides in vivo and that this property could underlie its association with autoimmune disease.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Townsend, A. & Bodmer, H. A. Rev. Immun. 7, 601–624 (1989).
Chen, B. P. & Parham, P. Nature 337, 743–745 (1989).
Bouillot, M. et al. Nature 339, 473–475 (1989).
Frelinger, J. A., Gotch, F. M., Zweerink, H., Wain, E. & McMichael, A. J. J. exp. Med. 172, 827–834 (1990).
Choppin, J. et al. J. exp. Med. 172, 889–899 (1990).
Chen, B. P., Rothbard, J. & Parham, P. J. exp. Med. 172, 931–936 (1990).
Huet, S. et al. Int. Immun. 2, 311–316 (1990).
Storkus, W. J., Howell, D. N., Salter, R. D., Dawson, J. R. & Cresswell, P. J. Immun. 138, 1657–1659 (1987).
Van Bleek, G. M. & Nathenson, S. G. Nature 348, 213–216 (1990).
Falk, K., Rötzschke, O. & Rammensee, H.-G. Nature 348, 248–251 (1990).
Rötzschke, O. et al. Nature 348, 252–254 (1990).
Nixon, D. F. et al. Nature 336, 484–487 (1988).
McMichael, A. J., Gotch, F. M. & Rothbard, J. J. exp. Med. 164, 1397–1406 (1986).
Rock, K. L., Rothstein, L. E., Gamble, S. R. & Benacerraf, B. Proc. natn. Acad. Sci. U.S.A. 87, 7517–7521 (1990).
Vitiello, A., Potter, T. A. & Sherman, L. A. Science 250, 1423–1426 (1990).
Kozlowski, S. et al. Nature 349, 74–77 (1991).
Nuchtern, J. G., Bonifacino, J. S., Biddison, W. E. & Klausner, R. D. Nature, 339, 223–226 (1989).
Yewdell, J. W. & Bennink, J. R. Science 244, 1072–1075 (1989).
Townsend, A. et al. Nature 340, 443–448 (1989).
Cerundolo, V. et al. Nature 345, 449–452 (1990).
Lie, W-R. et al. Nature 344, 439–441 (1990).
Ljunggren, H-G. et al. Nature 346, 476–480 (1990).
Townsend, A. et al. Cell 62, 285–295 (1990).
Schumacher, T. N. M. et al. Cell 62, 563–567 (1990).
Klar, D. & Hämmerling, G. J. EMBO J. 8, 475–481 (1989).
Brewerton, D. A. et al. Lancet I, 904–907 (1973).
Schlosstein, L., Terasaki, P. I., Bluestone, R. & Pearson, C. M. New Engl. J. Med. 288, 704–706 (1973).
Benjamin, R. J. & Parham, P. Immun. Today 11, 137–142 (1990).
Barnstable, C. J. et al. Cell 14, 9–20 (1978).
Lopez de Castro, J. A. Immun. Today 10, 239–246 (1989).
Kunkel, T. A. Proc. natn. Acad. Sci. U.S.A. 82, 488–492 (1985).
Salter, R. D., Clayberger, C., Lomen, C. E., Krensky, A. M. & Parham, P. J. exp. Med. 166, 283–288 (1987).
Ways, J. P. & Parham, P. Biochem. J. 216, 423–432 (1983).
Ellis, S. A., Taylor, C. & McMichael, A. Hum. Immun. 5, 49–59 (1982).
McMichael, A. J., Parham, P., Rust, N. & Brodsky, F. Hum. Immun. 1, 121–129 (1980).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Benjamin, R., Madrigal, J. & Parham, P. Peptide binding to empty HLA-B27 molecules of viable human cells. Nature 351, 74–77 (1991). https://doi.org/10.1038/351074a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/351074a0
This article is cited by
-
The peptide binding specificity of HLA-B27 subtypes
Immunogenetics (1994)
-
CD8 and β2-microglobulin-free MHC class I molecules in T cell immunoregulationMHC class I molecules in T cell immunoregulation
International Journal of Clinical & Laboratory Research (1993)
-
The pathogenetic aspects of spondyloarthropathies from the point of view of HLA-B27
Rheumatology International (1992)
-
The structure of HLA-B27 reveals nonamer self-peptides bound in an extended conformation
Nature (1991)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.
