IMMUNOBIOLOGY OF THE MAJOR HISTOCOMPATIBILITY COMPLEX

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The recent findings that many more class I genes may be present within the major histocompatibility complex (MHC) than previously thought, and the emerging evidence that many of these genes encode tissue differentiation antigens, some of which may function in cell recognition outside the immune system, make it appropriate to look more intently at differentiation antigens, some of which may function in cell recognition outside the immune system, make it appropriate to look more intently at differentiation antigens encoded by the MHC. Among these differentiation antigens are highly polymorphic erythroid cell antigens encoded by the chicken MHC. These enigmatic antigens, the B-G antigens, have formed the basis of MHC typing in chickens from the time that the chicken MHC or B system of histocompatibility was first identified. We have purified and analyzed the B-G antigen from the one haplotype, B21, and have found evidence that B-G antigens may be unusual variants of MHC class I molecules. I propose to determine the molecular structure of the B-G 21 antigen in order to better understand the similarities and differences which exist between these polymorphic differentiation antigens and class I transplantation antigens. Microsequencing, tryptic peptide mapping and gene sequencing will be used to determine the structure of the B-G 21 antigen. Genomic and cDNA libraries will be prepared from which the B-G21 antigen gene will be cloned. The B21 class I gene(s) will also be isolated using murine class I gene probes and the sequence of this gene used in the comparative analysis of B-G21. These two genes will be mapped with respect to each other. The low frequency of recombination between them indicates they are closer to each other than many elements within the murine MHC. The basis of the polymorphism of the B-G antigens will be examined using suitable recombinant DNA probes derived from the cloned B-G21 gene. These data will help us to understand the organization and evolution of the MHC.