This program will study the turnover and shedding of murine Major Histocompatibility class II class II antigens. Turnover rates and the mechanism of constitutive turnover of these proteins on B lymphocytes, antigen presenting cells, lymphomas and T cells (class 1) will be studied. Genetic influences on turnover will be examined to determine whether there is cis or trans genetic regulation of the turnover of class I antigens. The structure of shed class I and class II antigens will be examined and compared to membrane-associated antigens by 2D gel analysis, molecular sieving and peptide mapping. In general, cells will be radiolabeled by surface iodination or biosynthetic labeling. The cells will be cultured, extracted with non-ionic detergents and labeled antigens immunoprecipitated from lysates or culture supernatants (shed). Labeled cells will be cultured with interferon interleukins, or prostaglandins to determine the effects of these agents or turnover. This study will test the hypothesis that shed class I and class II antigens are identical to membrane- associated antigens and the information gained may provide insight into the role of shed MHC antigens in their function in the immune system.
