CELLULAR & MOLECULAR STUDIES OF LMP ANTIGENS & GENES

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The murine LMP antigens are a unique set of protein antigens ranging in molecular weight from 15-30,000 kilodaltons which are controlled by the major histocompatibility complex (MHC). Sixteen different LMP antigen polypeptides have been identified by two-dimensional gel electrophoresis, and two of these chains shown electrophoretic polymorphism; both of these polymorphisms map to the MHC, between the H-2K and I-A loci. All 16 of the LMP chains are associated with one another in a large, stable intracellular protein complex. Like the three previously described classes of MHC antigens, the expression of the LMP antigens is regulated by immune interferon (IFN-gamma), however, the LMP antigens are biochemically, serologically, and genetically distinct from MHC class I, II, and III antigens. The function of LMP complex and its relationship to other known MHC antigens is currently unknown. The project described herein utilizes two independent approaches for gathering clues to the function of this new class of MHC antigen. First, rabbit antisera made to purified murine LMP antigens will be used in immunohistochemical studies to determine the precise subcellular location of the LMP complex. Second, cloned DNA corresponding to LMP antigen subunits will be isolated from a set of previously isolated overlapping cosmid clones spanning the appropriate genetic region. These genomic clones will be used to isolate cDNA clones for a determination of the primary structure of the LMP antigens, and its comparison to other proteins of known function, especially the closely linked MHC class I and II antigens, tumor necrosis factor, and lymphotoxin. It is expected that knowledge of the primary structure and intracellular location of the LMP complex will yield clues to its biological function, and will permit the design of specific biological assays to test such possible functions.