The overall objective of this proposal is to investigate the structure, function, and control of expression of a number of molecules expressed on human lymphocytes and their subsets. We will investigate the molecular basis for structural and serological variations in the leukocyte differentiation antigen T200 or common leukocyte antigen between different leukocyte and lymphocyte types. We propose to isolate a membrane lectin expressed on lymphoblastoid cell lines and activated T-lymphocytes and study it's role in cell-cell interaction T-cell mediated killing. We propose to investigate the mechanisms of control of the expression of T200, HLA-DR antigens, and T-cell class and subclass specific membrane antigens by determining whether or not they are expressed, and the molecular basis for their expression on somatic cell hybrids. These will be produced by fusion of HGPRT-negative, ouabain-resistant T-lymphoblastoid lines (LCL) with other T-LCL expressing different surface antigens, with B-LCL, and with peripheral blood T and B-cells, resting or activated by mitogens and in the mixed lymphocyte response (MLR). We will attempt to generate cytotoxic hybrids of T-LCL with MLR-activated T-cells, determine their specificity for HLA antigens and characterize their antigen receptor. We propose to generate hybrids of T-LCL with MLR-activated cells which secrete non-immunoglobulin molecules which will bind to the HLA-A, B and C antigens of either the responder or the donor, to structurally characterize these molecules, and to determine their reactivity with human alloantisera recognizing Ia-like antigens. These hybrids and their products will be assayed for their ability to enhance or suppress the MLR and for the specificity of their effects in terms of the major histocompatibility complex antigens of both the responder and stimulator.
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