Mouse Cytolytic T Lymphocytes Induced by Xenogeneic Rat Stimulator Cells Exhibit Specificity for H-2 Complex Alloantigens

When mouse spleen cells were stimulated with irradiated xenogeneic, allogeneic, or trinitrophenyl-modified syngeneic lymphoid cells, the strongest cytolytic response was induced by alloantigens. Mouse cytolytic T lymphocytes generated to rat lymphoid cells demonstrated specificity for the immunizing rat strain, but extensive lysis of allogeneic target cells from certain mouse strains was also observed. Cold target inhibition studies indicated that separate clones of xenoantigen-induced cytolytic T lymphocytes lysed each of the allogeneic murine targets. [3H]Thymidine suicide of the effector cells generated to the rat stimulators revealed that only some of all potentially reactive mouse cytolytic T lymphocyte precursors with specificity for a given allogeneic target are activated by the stimulation with rat cells. This evidence that xenoantigens induce alloreactive cytolytic T lymphocytes is discussed in light of our proposal that the cytolytic T lymphocyte receptor repertoire is directed at variants of autologous major histocompatibility complex antigens.