Comparison between the Specificity of Primary and Secondary Killer Cells against Alloantigens and Hapten‐modified Syngeneic Lymphoid Cells

Cytotoxic responses of lymphoid cells from different mouse strains against syngeneic cells modified with the haptens fluorescein isothiocyanate and trinitrophenyl were investigated. Mice of the H‐2 k strain demonstrated strong primary in vitro hapten‐specific cytotoxicity reactions, which were H‐2 restricted and involved the K k specificity. However, cells from H‐2 d and H‐2 b mice developed hapten‐specific cytotoxic reactions that showed H‐2 cross‐reactivity. This cross‐reactivity, with regard to the restriction element, was particularly evident with cells from mice that had been immunized in vivo. No cross‐reaction was observed between the two haptens, however. Genetic mapping experiments demonstrated that cross‐reactions existed between D b and D d target cell antigens. Similar cross‐reactions were demonstrated in in vitro experiments in which secondary in vitro responses were induced by stimulation with cross‐reacting H‐2 antigens. This finding was also investigated in allogeneic cytotoxicity. In vitro induced responses resulting in relatively weak specific cell‐mediated lympholysis reactions were H‐2 specific, whereas secondary in vitro responses demonstrated cross‐reactivity between D d and D b antigens. In these test systems, cross‐stimulation was also demonstrated in secondary in vitro responses. These results are discussed in terms of similarities of T cell recognition of hapten‐modified self antigens and of alloantigens.