Genetic control of the immune response to insulin: its dependence upon a macrophage mediated selection of distinct antigenic sites.

The immune response to insulin, in both mouse and guinea pig , is under control of H-linked immune response genes. When immunized with either pork or beef insulin to CFA, both strain 2 and 13 guinea pigs respond by antigen-specific lymphocyte proliferation and synthesis of specific antibody. The specificity of the elicited antibodies are indistinguishable between these inbred strains. By contrast, strain 2 T cells recognize a distinct region of the A chain alpha loop consisting of amino acids residues 8, 9 and 10, while strain 13 T cells see an as yet undefined region of the B chain. H2b (A chain alpha loop responder) and H2d (B chain responder) mice similarly discriminate which area of the molecule are recognized by their T lymphocytes. The function of the Ir gene, in both the guinea pig and mouse appears to be an intramolecular selection of discrete regions within the antigen for recognition by the T cell. The data presented suggest that this function operates at the level of the macrophage.