Ir Gene Control of Cytolytic T Lymphocytes Induced by TNP Modified Syngeneic Cells in Normal and Chimeric Mice

Cytolytic T lymphocytes (CTL) generated to trinitrophenyl (TNP) modified syngeneic cells from mice bearing the H-2 b,d,r,s haplotypes exhibit cytolytic activity toward TNP modified syngeneic target cells, however they also demonstrate significant levels of cross reactive lysis of TNP modified allogeneic targets. In contrast, CTL from strains bearing the H-2 k haplotype are H-2 restricted, only lysing TNP modified syngeneic targets. This inability to cross-reactively lyse TNP modified allogeneic targets is a defect of the responder cell and not the stimulator. Specifically, (B6 × C3H)F 1 spleen cells demonstrate cross-reactive lysis when stimulated by either TNP modified C57BL/6 or TNP modified C3H stimulator cells. Utilizing H-2 recombinant strains we have mapped the genes controlling this H-2 retriction to the K and/or IA loci. Thus, this appears to be an Ir gene-like phenomenon. Bone marrow cells from C3H mice were allowed to mature in a lethally irradiated (B6 × C3H)F 1 host to determine whether the host environment influenced CTL specificity.