Regulation of immune response to tumor antigen: interference with syngeneic tumor immunity by anti-IA alloantisera.

We present evidence for a role of I-A subregion-encoded determinants in syngeneic tumor immunity. In animals rendered immune to the S1509a fibrosarcoma, daily treatment with microliter quantities of antisera directed against Kk and I-Ak determinants expressed on lymphoid cells of host origin decreased the capacity for immune tumor rejection. Absorption studies revealed that anti-I-Ak antibody activity alone was sufficient for the manifestation of this effect. Furthermore, experiments utilizing F1 hybrids showed that an antiserum that was genetically unable to interact with H-2 determinants expressed on the tumor was equally effective in inhibiting tumor immunity. Suggestive evidence that the activity of this antiserum is related to interference with the generation of effector T cell function was provided by the observation that hyperimmune animals pretreated with an anti-Kk,I-Ak antiserum were no longer capable of adoptively transferring tumor immunity to naive recipients. Thus, it is possible to regulate the secondary immune response to tumor antigens by using antisera with specificity for I-A determinants expressed on cells or possibly on factors of the host lymphoid system.