This work addresses the currently critical problems in rat immunogenetics and is a continuation of our long-term objective of defining the structure and function of the major histocompatibility complex in the rat. We have five specific aims: (1) The mapping of the MHC will continue with the search for new recombinants, the use of monoclonal antibodies, the definition of the alleles at RT1.E and the identification of Qa/T1a-like antigens. (2) The difference between membrane content and cell surface expression of MHC antigens and its genetic control will be studied. (3) The class I MHC antigens will be isolated from solubilized membrane preparations by affinity chromatography using monoclonal antibodies, and their differences will be defined by peptide mapping using HPLC. The class II antigens will be studied in the same way later. (4) The genetic and biochemical properties of neuraminidase will be studied to define the number of loci affecting its phenotype, its relationship to other hydrolases and the biochemical properties of its isozymes. (5) The chromosomes carrying the MHC and the other cell surface antigens RT2, RT3, and RT8 (Pta) will be identified. The methodology used includes breeding studies involving congenic, recombinant and inbred rats; the production, characterization and use of monoclonal antibodies; the isolation of cell surface antigens and their peptide mapping by HPLC; the biochemical definition of the neuraminidase isozymes, and the techniques of somatic cell genetics. The scientific disciplines involved are immunogenetics, immunochemistry, enzymology, and cytogenetics. It is important to study the genetics of the MHC in a species other than the mouse, so that the generality of the genetic mechanisms that it controls and its comparative genetics and evolution may be delineated. The research described here will also provide the essential genetic information for studies of MHC functions in organ transplantation, reproduction and oncology. (CS)
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