Studies in man are proposed in this grant request relating to the immunogenetics of the Major Histocompatibility Complex, HLA, and T lymphocyte responses to HLA-encoded antigens. Major emphasis is placed on the cloning of functionally-disparate T lymphocyte subpopulations. Cells of these clones will be used to study, at this very fine level of discrimination, the genetic control by HLA of determinants recognized by different T lymphocyte subpopulations; major effort will focus on the HLA-D region. Cloned populations will be evaluated as to function, cell surface markers (utilizing xenogeneic monoclonal anti-T lymphocyte sera, allo-anti-DR sera and the phenotype for a family of large membrane proteins (LMPs) and for interactions between the various types of cells (and their factors) in the overall in vitro cell-mediated immune response to alloantigens. Three related areas of investigation, which represent a very much smaller percentage of the total effort (and funds requested) include the following. First, study of the LMPs present on cells of different cloned populations with regard to their banding patterns on SDS/PAGE gel, their oligopeptide composition and polymorphism. Second, application of immunogenetic knowledge gained with cloned primed lymphocyte typing (PLT)-reactive cells in an attempt to define better markers for matching donor and recipient for kidney transplantation. Third, study of HLA antigen sharing between parents in families in which one or more individual is affected with a cranio-facial abnormality or in which the mother has had multiple spontaneous abortions.
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