Role of major and minor histocompatibility antigens in the suppression of alloreactive cytotoxic responses induced by alloantigen pretreatment.

We have recently shown that priming mice with allogeneic strain A spleen cells before immunization with (A x B)F1 spleen cells strongly suppresses the cytotoxic T-lymphocyte (CTL) response directed against linked strain B alloantigens. This specific decrease in the CTL responses against the second immunizing alloantigen is associated with a high CTL response against the first priming alloantigen. The suppression of CTL responses against the strain B alloantigens is, however, not due to killing of F1 spleen cells by anti-A CTL, since it was observed after immunization of primed mice with a mixture of (A x B)F1 and B cells. In the present study, attempts were made to determine the relative contribution of H-2 and minor histocompatibility background antigens towards induction of suppression. Our results demonstrate that priming and immunizing spleen cells have only to share H-2 antigens in order to induce a downregulation of CTL responses directed against the linked alloantigens. This indicates that immunity against H-2 antigens is sufficient to induce suppression. However, priming against minor histocompatibility antigens also induces suppression, but only if spleen cells used for priming and immunization share H-2 antigens with the recipient strain. Therefore, the suppression can be induced by priming with non-H-2 antigens but is H-2-restricted. This study has also demonstrated that suppression can be induced by intraperitoneal or subcutaneous administration of allogeneic cells.