Hugh McDevitt

Hugh McDevitt, Professor Microbiology and Immunology; Medicine Stanford University School of Medicine, Fairchild D345, Stanford, CA 94305-5124 Tel: (650) 723-5893 FAX: (650) 723-9180

(i) Analysis of the structure and functional characteristics of the Class II major histocompatibility antigens which regulate the specificity and intensity of the immune response to a variety of protein antigens. This involves cDNA cloning and sequence analysis, site specific mutagenesis and injection of the resultant mutants into embryos to produce transgenic mice, and attempts to achieve high level expression of Class II antigens for characterization of their structure by the techniques of proteins chemistry and protein crystallography.

(ii) Attempts to correlate Class II MHC genetic polymorphism with susceptibility and resistance to a wide variety of autoimmune diseases.

(iii) The use of monoclonal antibodies, as well as other strategies, to alter the expression and/or function of Class II MHC antigens in order to down regulate the allele-specific immune response and thus develop new strategies for treating autoimmune disease. (Projects ii, iii and iv apply to a wide variety of autoimmune diseases including rheumatoid arthritis, diabetes mellitus, multiple sclerosis, and many others.

(iv) Analysis of the role of MHC Class II genes in presenting self antigens in the autoimmunity seen in Type I insulin-dependent diabetes mellitus and in experimental allergic encephalomyelitis.

Smilek, D.E., Wraith, D.C., Hodgkinson, S., Dwivedy, S., Steinman, L. and McDevitt, H.O. (1991). A single amino acid change in a myelin basic protein peptide confers the capacity to prevent rather than induce experimental autoimmune encephalomyelitis. Proc Natl Acad Sci USA 88:9633-9637.
Gautam, A.M., Pearson, C.I., Smilek, D.E., Steinman, L., and McDevitt, H.O. (1992). A Polyalanine peptide with only five native myelin basic protein residues induces autoimmune encephalomyelitis. J Exp Med 176:605-609.
Singer, S.M., Tisch, R., Yang, X.-D., and McDevitt, H.O. (1993). Protective Class II MHC Alleles Prevent Diabetes in NOD Mice by Altering T Helper Cell Subsets. Submitted.
Tisch, R., Yang, X.-D., Singer, S.M., Liblau, R.S., Fugger, L., and McDevitt, H.O. (1993). Immune Response to Glutamic Acid Decarboxylase Coincides with Insulitis Onset in Non-Obese Diabetic Mice. Submitted.

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