The experiments all aim to understand the relationship between major histocompatibility haplotype and the binding of ligands to specific cell surface receptors. Two different systems of ligand receptor binding will be studied for effects of H-2 and HLA on binding. Peptide hormone binding to fibroblasts, fat cells and liver membranes will be studied as a function of H-2 type in order to extend our previous observations on glucagon and insulin binding. The new experiments will concentrate on glucagon, insulin and epidermal growth factor (EGF) binding and thus the results will be extended to new cell types and to a hormone not previously studied by us, EGF. In addition, we will examine the effect of monoclonal anti-H-2 antibodies on peptide hormone binding. Some fluorescent-labelled antibodies and hormones will be used to determine the proximity of peptide hormone receptors and MHC antigens on cell membranes. We except that a monoclonal anti-HLA and EGF will be the most suitable combination for initial experiments, since we have shown a functional interaction between these two cell surface components. Cell-cell adhesion is the second system of receptor-ligand interactions to be studied as a function of H-2 type. We will use a new assay for the determination of adhesion rates of intact fibroblasts to one another. We will also use monoclonal anti-H-2 antibodies to perturb this adhesion system and another in which single cells adhere to a monolayer. All of these experiments should help to better define the function of class I MHC antigens in cells other than those of the immune system.
