Non-obese diabetic (NOD) mice spontaneously develop diabetes resembling human IDDM. In both humans and NOD mice, susceptibility to diabetes is strongly associated with genes of the major histocompatibility complex (MHC). Since MHC class II cells, it is possible that a common mechanism for murine and human diabetes is reflected in this association. Of particular interest to the hypothesis underlying the experiments outlined in this grant application was the demonstration that T cells, which transfer experimental allergic encephalomyelitis from one animal to another, were shown to have receptors whose variable domains were encoded by a limited and highly homologous set of V region gene segments. The presumption (hypothesis) underlying this grant application is that in experimental, as well as human insulin dependent diabetes mellitus (IDDM), a similar limited repertoire of will be examined under the specific aims listed below. Demonstration of a limited repertoire of T cell receptors will allow development of immunotherapeutic protocols. Synthetic peptides, corresponding to the CDR1 or CDR2 germ line encoded regions of the T cell receptor V region products of interest, will be utilized in vaccination strategies to block the induction of autoimmune disease in NOD mice. Potential islet autoantigens in NOD mice will be analyzed using nitrocellulose immunoblots to subdivide antigens recognized by infiltrating T lymphocytes based upon their apparent molecular weight. T cell clones and/or hybridomas will be produced if specific reactivity can be demonstrated. The five specific aims listed in this grant application intend to question whether more specific forms of immunotherapy can be developed. This is based upon the hypothesis underlying this grant application that the autoimmune beta cell destruction in NOD mice will express a limited repertoire of T cell receptor V region gene products and can be targets of immunotherapeutic intervention.
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