Our laboratory has a long standing interest in development of immunochemical methods for cell separation, for studying receptor-mediated activation of T cells, and in the role of T cells in tumor rejection. With respect to immune activation, we are particularly interested in developing methods for the direct measurement of the interaction of the T cell receptor with MHC antigens. As an outgrowth of these interests, we have recently been developing methods for constructing semisynthetic multivalent macromolecular reagents, for which we have coined the term """"""""polygens"""""""". Polygens are high molecular weight soluble polymers conjugated to proteins such as antigens, antibodies, toxins, or lymphokines. We believe that polygens, by increasing the effective valence of protein epitopes, may help to measure low affinity molecular interactions such as that between the T cell receptor and MHC antigens, and that such studies may help us understand the molecular requirements for activation of T cells. During this year we have used our general reagent Polyacrylamide-Streptavidin (PASA) to elicit a T-independent response to the native epitopes of streptavidin. We continued to develop polyvalent conjugates of Class I MHC antigens for use in studying interactions with T cell receptors. In addition, we have prepared polyvalent conjugates of the CD4 receptor for HIV. Such conjugates can bind the viral gp12O protein, and can inhibit HIV infection as measured by the syncytium assay.