H-2 restriction: independent recognition of H-2 and foreign antigen by a single receptor.
We describe two situations in which the recognition of hapten can compensate for the lack of recognition of appropriate H-2 gene products in hapten-specific, H-2 restricted, T lymphocyte-mediated cytolysis. First, we show that although recognition of appropriate H-2 gene products is essential for the lysis of target cells bearing a low hapten density, significant hapten-specific lysis of H-2 inappropriate target cells is observed at high levels of target cell derivatization. Secondly, we show that hapten-conjugated anti-H-2 antibody inhibits cytolysis poorly even though its binding to target cell H-2 antigens is equivalent to that of underivatized antibody. These results suggest that hapten and H-2 are recognized independently and are therefore inconsistent with the altered-self model. Although our data do not exclude the dual-recognition model, we prefer to interpret them within the framework of a single-receptor model in which hapten and H-2 are recognized independently by receptors of identical idiotype on the T cell. We postulate that the affinity of these receptors for the relevant H-2 gene product is low enough so that the T cell is not activated by encounters with normal-self cells expressing that H-2 gene product. However, when self cells express in addition a foreign antigen that can also be recognized by the same receptor, then the force of T cell-target cell interaction may be increased sufficiently to activate T cell effector function.
D000818:Animals; D000937:Antigen-Antibody Reactions; D003602:Cytotoxicity, Immunologic; D004306:Dose-Response Relationship, Immunologic; D006183:H-2 Antigens; D006241:Haptens; D007130:Immunoglobulin Idiotypes; D007518:Isoantibodies; D008297:Male; D051379:Mice; D009578:Nitrobenzenes / Q000276:immunology*; D011971:Receptors, Immunologic / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014301:Trinitrobenzenes / Q000276:immunology*
D006183:H-2 Antigens; D006241:Haptens; D007130:Immunoglobulin Idiotypes; D007518:Isoantibodies; D009578:Nitrobenzenes; D011971:Receptors, Immunologic; D014301:Trinitrobenzenes