The human B cell alloantigens expressed on molecules resembling the murine la system will continue to be studied. Utilizing monoclonal antibodies and pregnancy alloantibodies, novel la alloantigenic specificities will be delineated in particular normal individuals or populations of individuals with diseases in which susceptibility is influenced by la allotypes. Principal emphasis is placed on the recognition of la determinants that may arise through chain interaction and other post translational events, reflect the products of multiple loci, or are restricted in their expression to special lineages. Certain of these may be candidates for IR gene products. The molecular basis and relationships of these antigens will be characterized on the cell surface and on solubilized molecules using binding experiments and sequential immunoprecipitation. The inheritence of the novel specificities will be examined in family studies, and in pedigrees with multiple instances of particular MHC-linked diseases. The observation that certain stimuli activate T cells or monocytes to distinct phenotypes characterized by abundant or negligable la expression will be studied from the view of la biosynthesis, its control and the properties of the shed product. The properties of la+ T cells will receive special study. The function of la molecules, and in particular those bearing novel alloantigens, will be approached in the immune system using an antigen presenting system and in normal and leukemic developmental hematopoiesis where the role of la as a molecule possibly involved in the control of cell proliferation is independent of an immune response. Attempts to define the domains of the la molecule critical to recognition will be made by inhibition and binding experiments. Approahces will be made towards defining the nature of the process of uptake of exogenous la molecules by T cells and whether a restricted complementary anti la receptor can be identified on these cells by ligand receptor interactions.
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