Inserted H–2 gene membrane products mediate immune response phenotype of antigen-presenting cell

Abstract

Soluble protein antigens do not stimulate helper or effector T lymphocytes unless they have first been processed and exposed to the T lymphocytes by appropriate antigen-presenting cells. This antigen presentation was found to be controlled by products of genes in the major histocompatibility complex (MHC), designated H–2 in the mouse. Efficient antigen presentation to T lymphocytes is obtained only when both presenting and responding cells share alleles within the I region of the MHC¹. Furthermore, immune response (Ir) genes in the MHC influence the choice of antigenic determinants recognized on the immunogenic molecule². To investigate the molecular mechanisms underlying Ir gene expression, we have inserted membrane components isolated from cells of one Ir genotype into recipient cells of a different Ir genotype, using membrane vesicles composed of donor plasma membranes and envelope glycoproteins from Sendai virus³. We now report that this ‘membrane-engineering’ enables genetically inappropriate antigen-presenting cells to communicate to T lymphocytes antigenic determinants of beef or sheep insulins, antigens under control of Ir genes in mice⁴. This demonstrates that structural products of MHC genes, expressed and active at the plasma membrane, function in the Ir phenotype of the response to insulin.