On the role of the H 2 histocompatibility complex in determining the specificity of cytotoxic effector cells sensitized against syngeneic trinitrophenyl modified targets

Spleen cells cultured with syngeneic TNP modified stimulator cells display a cytotoxic effect against syngeneic TNP modified targets, but not against modified targets from unrelated H-2 haplotypes. Targets that share the K and I region of the H-2 complex with the stimulator (or effector) cells are lysed to the same extent as the specific targets, while targets that share the I region only are not. When only the D region is shared, a weak cytotoxic effect is observed. Therefore, the stimulator (or effector) and target cell must share the K or D but not the I region of the H-2 complex in order for optimal cytotoxicity to occur. Spleen cells sensitized to irradiated TNP modified H-2 allogeneic cells are cytotoxic to these specific targets, but not against TNP modified targets syngeneic with the effector cells. Coculture of F₁ hybrid cells with irradiated TNP modified parental cells results in a cytotoxic effect against only those specific parental cells and not TNP modified cells from the other parent. The cytotoxic effect of the F₁ effector cells in the cell mediated lympholysis test is blocked by the addition of unlabeled TNP modified targets that are H-2 syngeneic with the sensitizing parental strain, but not H-2 syngeneic with the other parental strain. These data demonstrate that the specificity of the effector cell in this syngeneic cytotoxicity system is directed against altered self H-2 controlled gene products, rather than a requirement for sharing of histocompatibility genes between effector and target cell in order for lysis to occur. The role of H-2 antigens in determining the sensitivity of a target cell to T cell mediated lysis is discussed.