The overall objective of the research proposed in this application is the elucidation of the detailed structure of two sets of gene products encoded by the H-2 complex, the major histocompatibility complex (MHC) of the mouse. The gene products to be studied, the H-2K and Ia antigens, are both highly polymorphic sets of glycoprotein molecules integrated in the lymphocyte plasma membrane. The studies proposed in this application should lead to a thorough knowledge of the primary structure of both the protein and carbohydrate portions of these antigens. For the H-2K antigens, the proposed studies involve large scale biochemical purification, amino acid sequence determination, and carbohydrate structure determination. For the Ia antigens, biosynthetic radiolabeling will be combined with immunochemical purification; the materials thus isolated will have their amino acid sequences and carbohydrate structures determined by radiochemical methods. Comparative analysis of amino acid sequence data (employing data obtained in other laboratories as well as our own) will be exploited to try to deduce the antigenically significant portions of these molecules. In addition, experiments will be carried out which approach this problem directly, either through the use of tryptic or cyanogen bromide fragments (of known structure) to inhibit the binding of alloantisera to intact antigens, or through the use of alloantisera to block reaction of protein modification reagents with the antigenic site. Cross-linking studies will be carried out to try to elucidate interactions of H-2 and Ia antigens with other molecules in the lymphocyte plasma membrane. Finally, experiments will be undertaken to try to establish the molecular function of the H-2 antigens in "H-2 restricted" anti-viral cytotoxicity; and to examine the function(s) of the Ia antigens in I region regulated antigen presentation systems in vitro.