Abstract
IN antigen-presenting cells, class II molecules of the major histocompatibility complex (MHC) bind peptides derived from endo-cytosed proteins1. In certain B-lymphoblastoid cell mutants, MHC class II molecule–peptide complex formation is impaired, resulting in deficient antigen-presenting function2. MHC deletion mutants with this defect map the responsible gene(s) to the class II region of the MHC3–5. Here we report that multiple independent mutants with the class II presentation defect harbour lesions in HLA-DMB, an MHC-linked gene encoding a class II-like β-chain6,7. Expression of DMB complementary DNA in mutants lacking DMB messenger RNA restores the wild-type phenotype. These results establish HLA-DM as a critical regulatory molecule in class II-restricted antigen presentation and suggest that it functions at an intracellular site to promote class II molecule–peptide association.
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
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
References
Rudensky, A. Y., Preston-Hurlburt, P., Hong, S.-C., Barlow, A. & Janeway, C. A. Jr Nature 353, 622–626 (1991).
Mellins, E. et al. Nature 343, 71–74 (1990).
Mellins, E., Kempin, S., Smith, L., Monji, T. & Pious, D. J. exp. Med. 174, 1607–1615 (1991).
Riberdy, J. M. & Cresswell, P. J. Immun. 148, 2586–2590 (1992).
Ceman, S., Rudersdorf, R., Long, E. O. & DeMars, R. J. Immun. 149, 754–761 (1992).
Cho, S., Attaya, M. & Monaco, J. J. Nature 353, 573–576 (1991).
Kelly, A. P., Monaco, J. J., Cho, S. & Trowsdale, J. Nature 353, 571–573 (1991).
Pious, D., Dixon, L., Levine, F., Cotner, T. & Johnson, R. J. exp. Med. 162, 1193–1207 (1985).
Mellins, E. et al. J. exp. Med. 179, 541–549 (1994).
Riberdy, J. M., Newcomb, J. R., Surman, M. J., Barbosa, J. A. & Cresswell, P. Nature 360, 474–477 (1992).
Sette, A. et al. Science 258, 1801–1804 (1992).
Hunt, D. F. et al. Science 256, 1817–1820 (1992).
Chicz, R. M. et al. J. exp. Med. 178, 27–47 (1993).
Spies, T. et al. Nature 348, 744–747 (1990).
Brown, J. H. et al. Nature 364, 33–39 (1993).
Cammarota, G. et al. Nature 356, 799–801 (1992).
Konig, R., Huang, L-Y. & Germain, R. N. Nature 356, 796–798 (1992).
Cosgrove, D. et al. Cell 66, 1051–1066 (1991).
Grusby, M. J., Johnson, R. S., Papaioannou, V. E. & Glimcher, L. H. Science 253, 1417–1420 (1991).
Griffith, I. J. et al. J. exp. Med. 167, 541–555 (1988).
Sant, A. J. & Chervonsky, A. Hum. Immun. 37s, 3 (1993).
Campbell, R. D. & Trowsdale, J. Immun. Today 14, 349–352 (1993).
Johnson, J. P., Meo, T., Riethmuller, G., Schendel, D. J. & Wank, R. J. exp. Med. 156, 104–111 (1982).
Gladstone, P., Fueresz, L. & Pious, D. Proc. natn. Acad. U.S.A. 79, 1235–1239 (1982).
Gladstone, P. & Pious, D. Nature 271, 459–461 (1978).
Xie, W. & Rothblum, L. I. BioTechniques 11, 325–327 (1991).
Lampson, L. A. & Levy, R. J. Immun. 125, 293–299 (1980).
Mellins, E., Woelfel, M. & Pious, D. Hum. Immun. 18, 211–223 (1987).
Johnson, A. H. et al. in Immunobiology of HLA (ed. Dupont, B.O.) 202–203 (Springer, New York, 1984).
Shaw, S., Johnson, A. & Shearer, G. J. exp. Med. 152, 565–580 (1980).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Morris, P., Shaman, J., Attaya, M. et al. An essential role for HLA–DM in antigen presentation by class II major histocompatibility molecules. Nature 368, 551–554 (1994). https://doi.org/10.1038/368551a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/368551a0
This article is cited by
-
Ancient features of the MHC class II presentation pathway, and a model for the possible origin of MHC molecules
Immunogenetics (2019)
-
A personal retrospective on the mechanisms of antigen processing
Immunogenetics (2019)
-
Genetics of antigen processing and presentation
Immunogenetics (2019)
-
What to do with HLA-DO/H-2O two decades later?
Immunogenetics (2019)
-
Footprints of antigen processing boost MHC class II natural ligand predictions
Genome Medicine (2018)
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.