POLYMORPHIC NEURONAL SURFACE PROTEINS

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Many proteins that serve recognition functions outside the nervous system belong to the same family of structurally-related molecules, the HIBIT (HLA, Ia, b2-microglobulin, immunoglobulin, Thy-1) superfamily. Genetic studies show that still othe gene products of this family remain to be identified. Although this family has primarily been studied in lymphoid tissue, it is not limited to lymphoid tissue: Thy-1 is a major cell surface protein of neurons. We hypothesize that: (1) Some "new" HIBIT proteins are in the nervous system, and (2) like the other members of this family, they serve recognition functions. We will exploit techniques I have used previously, to reveal new HIBIT proteins in neural tissue. We will use monoclonal antibodies (MoAbs) to known HIBIT proteins to look for new variants. We will also raise MoAbs to cross-reactive intra-family determinants, to be used as more general probes for new HIBIT proteins. In general terms, our work will show how MoAbs may be used as probes for multi-gene families, particularly when conventional isolation and biochemical characterization of the molecules are difficult. This would apply to proteins present in small quantities, or cell types that cannot be separated, and must therefore be compared in microscopic assays. Our previous work illustrates the clinical relevance of this work: We have found weak HLA-A,B,C expression on human cells of neuronal origin, which has implications concerning the growth potential of neuronal tumors, and neural transplants. In later studies, we will determine the nature of possible polymorphisms (cell to cell, tissue to tissue, etc.) of new HIBIT proteins; this will suggest the type of recognition function each might serve.