This proposed research project involves the intensive study of histocompatibility alloantigens on cultured human tumor cell lines with special reference to serological and functional comparative tests in relation to the specificity of alloantigens on lymphocyte subpopulations from the tumor donors. Our laboratories have: Extensive experience with the technical aspects of HLA typing human tumor cell lines; a large number of available cell lines of diverse origin; normal tissues fibroblast cell lines, B-cell lines and fresh and frozen peripheral blood lymphocytes from the cell line donors; large numbers of highly selected allospecific HLA typing reagents that collectively define all the well-characterized HLA-A, B, C, DR, MB and MT antigens; large numbers of completely HLA typed normal panel cells, B-Cell type CLL cells and lymphoblastoid cell lines; and, a selection of monoclonal and allospecific antibodies to DR antigens, T-cell differentiation antigens and alloantigens expressed on activated T-cells. Our research objectives will be: 1) To establish the extent to which human tumor cell lines express genetically appropriate HLA alloantigens and the extent to which the expression of these antigens remains stable during cell culture and can be used to confirm the identity and purity of cell line cultures. 2) To study the functional role of the DR alloantigens expressed on certain human tumor cell lines, notably melanoma, as primary or secondary stimulators of allogeneic lymphocytes and to thereby help clarify the relationship between HLA-D and HLA-DR determinants which are respectively defined in relation to primary lymphocyte stimulation and serological reaction patterns. 3) To study the functional role of the DR alloantigens expressed on certain human tumor cell lines as stimulators and/or targets of cytotoxic allogeneic lymphocytes. 4) To determine whether certain human tumor cell lines may also express T-cell differentiation antigens or alloantigens expressed on activated T-cells and, if so, to analyze their serological and biochemical properties in comparison with cell line donor T-cell antigens. 5) To analyze the allospecificity of sera from patients receiving therapeutic vaccines containing syngeneic or allogeneic cultured tumor cell line extracts and to relate these alloantibody responses to immune responses to tumor antigens, patient HLA type, and clinical course.