Abstract
HUMAN leukocyte antigen (HLA)-DM is an unconventional major histocompatibility complex (MHC) class II heterodimer that is important for B-cell-mediated antigen processing and presentation to MHC class II-restricted T cells1–12. HLA-DM is encoded by two genes, DMA and DMB, which map to the MHC class II region1, and shares some homology with MHC class I and class II proteins2,3. Here we define the biochemical role of HLA-DM. Recombinant soluble HLA-DM heterodimers have been purified from culture supernatants of insect cell transformants. At pH 5.0, they induce the dissociation of a subset of peptides bound to HLA-DR, including a nested set of class-II-associated invariant chain peptides (CLIP). This process liberates HLA-DR and leads to the enhanced binding of exogenous peptides.
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
Kelly, A. P., Monaco, J. J., Cho, S. G. & Trowsdale, J. Nature 353, 571–573 (1991).
Denzin, L. K., Robbins, N. F., Carboy-Newcomb, C. & Cresswell, P. Immunity 1, 595–606 (1994).
Karlsson, L., Peleraux, A., Lindstedt, R., Liljedahl, M. & Peterson, P. A. Science 266, 1569–1573 (1994).
Riberdy, J. M., Newcomb, J. R., Surman, M. J., Barbosa, J. A. & Cresswell, P. Nature 360, 474–477 (1992).
Mellins, E., Kempin, S., Smith, L., Monji, T. & Pious, D. J. exp. Med. 174, 1607–1615 (1991).
Ceman, R. D., Rudersdorf, R., Long, E. O. & Demars, R. J. Immun. 149, 754–761 (1992).
Riberdy, J. M. & Cresswell, P. J. Immun. 148, 2586–2590 (1992).
Mellins, E. et al. Nature 343, 71–74 (1990).
Sette, A. et al. Science 258, 1801–1804 (1992).
Monji, T., McCormack, A. L., Yates, J. R. I. & Pious, D. J. Immun. 153, 4468–4477 (1994).
Morris, P. et al. Nature 368, 551–554 (1994).
Fling, S. P., Arp, B. & Pious, D. Nature 368, 554–558 (1994).
Amigorena, S., Drake, J. R., Webster, P. & Mellman, I. Nature 369, 113–120 (1994).
Peters, P. J., Neefjes, J. J., Oorschot, V., Ploegh, H. L. & Geuze, H. J. Nature 349, 669–676 (1991).
Qui, Y., Yu, X., Wandinger-Ness, A., Dalke, D. P. & Pierce, S. K. J. Cell Biol. 125, 595–605 (1994).
Sanderson, F. et al. Science 266, 1566–1573 (1994).
Tulp, A., Verwoerd, D., Dobberstein, B., Ploegh, H. L. & Pieters, J. Nature 369, 120–126 (1994).
West, M. A., Lucocq, J. M. & Watts, C. Nature 369, 147–151 (1994).
Hopp, T. P. et al. Biotechnology 6, 1205–1210 (1988).
MacArthur, H. & Walter, G. J. Virol. 52, 483–491 (1984).
Stern, L. J. & Wiley, D. C. Cell 68, 465–477 (1992).
Mellins, E. et al. J. exp. Med. 179, 541–549 (1994).
Buus, S., Sette, A., Colon, S. M., Jenis, D. M. & Grey, H. M. Cell 47, 1071–1077 (1986).
Sercarz, E. E. et al. A. Rev. Immun. 11, 729–766 (1993).
Nelson, C. A., Petzold, S. J. & Unanue, E. R. Proc. natn. Acad. Sci. U.S.A. 90, 1227–1231 (1993).
Nelson, C. A., Petzold, S. J. & Unanue, E. R. Nature 371, 250–252 (1994).
Germain, R. N. & Rinker, A. G. J. Nature 363, 725–728 (1993).
Lanzavecchia, A., Reid, P. A. & Watts, C. Nature 357, 249–252 (1992).
Bunch, T. A., Grinblat, Y. & Goldstein, L. S. B. Nucleic Acids Res. 16, 1043–1061 (1988).
Steller, H. & Pirrotta, V. EMBO J. 4, 167–171 (1985).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Sloan, V., Cameron, P., Porter, G. et al. Mediation by HLA-DM of dissociation of peptides from HLA-DR. Nature 375, 802–806 (1995). https://doi.org/10.1038/375802a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/375802a0
This article is cited by
-
Distinct editing functions of natural HLA-DM allotypes impact antigen presentation and CD4+ T cell activation
Cellular & Molecular Immunology (2020)
-
Synergy between B cell receptor/antigen uptake and MHCII peptide editing relies on HLA-DO tuning
Scientific Reports (2019)
-
Structure-based selection of human metabolite binding P4 pocket of DRB1*15:01 and DRB1*15:03, with implications for multiple sclerosis
Genes & Immunity (2019)
-
A personal retrospective on the mechanisms of antigen processing
Immunogenetics (2019)
-
Immune stimulation of rainbow trout reveals divergent regulation of MH class II-associated invariant chain isoforms
Immunogenetics (2019)
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.