The four main goals of this work are: (i) to map DNA of the human major histocompatibility complex (MHC); (ii) to isolate the functionally characterize a gene that is needed for expression of human class I HLA antigens; (iii) to create a collection of human B-lymphoblastoid cell lines each of which expresses just one specified class II antigen; (iv) to genetically map and characterize new human histocompatibility loci. Achievement of these goals will: (i) improve our understanding of the relations between MHC genes and many hereditary predispositions to diseases that show """"""""disease association with MHC loci; (ii) add to our knowledge of how expressions of class I antigens are regulated, which is important in relation to the body's defense mechanisms against virus infections and, possibly, malignancies; (iii) provide detailed knowledge about the relations between antibody recognition and T cell recognition of immune response antigens; (iv) add to our knowledge of the total repetoire of human immune responses. A collection of human B-lymphoblastoid cell line mutants from which different parts of the MHC have been deleted by gamma irradiation will be used. Goal (ii) will be achieved by transferring DNA from normal cells into cells that have a homozygous deletion of the class I-regulatory locus. DNA that restores expression of class I antigens to the mutants will then be cloned. Objective (iii) will be achieved by transferring specified single class II alpha and class II beta genes into mutant cells that have a homozygous deletion of all known class II genes. Goal (iv) will be achieved by preparing monoclonal antibodies and T cell clones that recognize lymphocyte-reactive antigens that remain on mutants that no longer express known class I and class II antigens.
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