Nonresponsiveness to the male antigen H-Y in H-2 I-A-mutant B6.C-H-2bm12 is not caused by defective antigen presentation.

The B6.C-H-2bm12 (bm12), H-2 I-Ab mutant, originated in the C57BL/6 (B6, H-2b) strain, is a nonresponder to the male antigen H-Y in both T cell proliferation and cytotoxic T lymphocyte (CTL) responses. Defective H-Y presentation by bm12-adherent cells, as a cause of the CTL nonresponsiveness, can be excluded, because 1) CTL from primed responder/nonresponder F1 female mice (B6/bm12 F1) were activated by H-Y antigen on antigen-presenting cells (apc) from either parent; 2) T cells from primed nonresponder bm12 females did not generate CTL to H-Y presented by responder B6 apc, but conversely, CTL from B6 females could be activated by antigen on bm12 apc; and 3) adherent cell-depletion experiments indicated that male adherent cells are necessary for generation of optimal H-Y-specific CTL responses, male adherent bm12 cells being equally as efficient as male adherent B6 cells in presentation to F1 T cells. The need for T helper cell activation by H-Y-presenting adherent cells during secondary in vitro restimulation can be circumvented by interleukin 2 (IL 2), because IL 2 completely restored the H-Y-specific CTL response of B6/bm12 F1 cells in cultures depleted of adherent cells. However, addition of IL 2 during in vitro restimulation of bm12 cells did not result in an H-Y-specific CTL response, indicating that H-Y-specific, I-A-restricted T helper cells are probably needed in vivo during priming for the generation of sufficient numbers of Db-restricted CTL memory cells. The data are compatible with the concept that H-Y antigen is presented in the context of the I-A alpha, beta molecule on the surface of adherent cells to T helper cells and in the context of the Db molecule on the surface of nonadherent as well as adherent cells to CTL precursors. The most likely explanation for the difference in H-Y response between B6 and bm12 include positive selection of the responder phenotype by the I-Ab alpha, beta molecule of the B6 strain or generation of suppressor T cells in the bm12 strain.