Molecular anatomy of immune recognition: How peptides bind to class I MHC molecules

IMMUNE REGULATION AND NEUKOIMMUNOLOGY MOLECULAR ANATOMY OF IMMUNE RECOGNITION: HOW PEPTIDES BIND TO CLASS I MHC MOLECL LES J a c k L. Stromingcr Depamncnt of Biochemist~ and Molecular Biology, Harvard University, Cambridge, MA., Dana-Farber Cancer Institute and Harvard Medical Schl. Boston, MA Foreign (for example, virus derived) and self pcptides are presented to effcctor T cells of the immune system by class I or class II molecules encoded in the major histocompatibility complex. The crystal sLructures of two alleles of tbe HLA-A locus (HI,A-A2 and HLA/,68) and of an isotype encoded at the HLA-B locus (HLA-B27) have now been elucidated and have revealed that the~ peptides are bound tightly in a cleft in the surface of the molecule. SG:ne of the amino acid side chains of the bound peptides arc fixed in pockets within the cleft. These recent studies together with definition of the pcptide nonamcxs bound to these molecules and the use of mutants of HLA-A2 have provided many details of the mechanism of peptide binding. (The studies presented wet< ca,~."ed out in collaboration with Drs. Don C. Wiley and Andrew McMichael and members of t'~h laboratories). 1. Bjorkman, PJ., S~per, M.A., Samraoui, B., Bcnnet, W.S., Strominger, I.L. and Wiley, D.C. Nature 1987; 329:506-512 and 512-518. 2. Garrett, T.PJ., Sapcr, M.A., Bjor~-nan, P..I., Strominger, J.L. and Wiley, D.C. Nature 1989; 342:692-696. 3. Gorga, I.C., Madden, D., Prendergast, J., Wiley, D.C. and Strominger, I.L. Proteins 1991; in press. 4. Madden, D., Gorga, J.C., Strominger, J.L. and Wiley, D.C. Nature 1991; in press. 5. Latron, F., Moots, R., Rothhard, J.B., Garrett, T.PJ., Wiley, D.C., Stromiager, J.L. and McMichael, A. Prec. Natl. Acad. Sci. USA 1991; in press.

MHC IN IMMUNOBIOLOGY AND NEUROIMMUNOLOGY Lawrence Steinman Stanford University School of Medicine Stanford, California 94305-5235 U.S.A. The critical role of the trimolecular complex of MHC-TCR and antigen will be described. Strategies for interfering with recognition of self-antigen have been successfully employed to treat neuroimmunologic disease. These apptoach~, including reagents targeting TCR V regions and MHC, will be reviewed. The induced expression of MHC genes in the nervous system will be discussed. New technologies have been employed to map the association of MHC and TCR genes with neuroimmunologic disease. These associations and their potential significance will be considered.

1