This application is for continued support of our efforts to characterize, at a molecular level, the class I gene family of the human major histocompatibility complex (MHC). The human MHC is designated the HLA complex. In addition to maintaining the transplantation barrier between individuals, molecules encoded by the MHC have a central role in regulating the immune response. MHC class I molecules are recognized together with foreign antigens at the cell surface of target cells by the receptor on cytotoxic T lymphocytes. Multiple genetic loci within the human MHC encode class I proteins. The experiments described in this proposal will focus on two interesting aspects of HLA class I molecular genetics. The molecular characterization of the non-A,B,C class I genes and their expression will be undertaken to provide insights into their function. A particularly intriguing question concerns a possible functional relationship between one or all of the HLA non-A,B,C class I molecules and cells expressing the gamma/delta receptor molecule. The second group of experiments will identify and characterize factors important in the regulation of HLA class I gene transcription. Regulation of class I gene expression is an important component in determining whether a cell can interact with T cells in a functionally significant manner.
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