Non-H-2-associated genetic regulation of cytotoxic responses to hapten-modified syngeneic cells. Effect on the magnitude of secondary response and helper T cell generation after in vivo priming

Abstract

The present study investigates the role of non-H-2 genes in controlling generation of the H-2-restricted, T cell-mediated cytotoxic response against trinitrophenyl (TNP)-modified syngeneic cells (TNP-self). Spleen cells from C3H/He (H-2k) or B10.BR (H-2k) normal mice or from mice primed to TNP in vivo by skin painting with trinitrochlorobenzene were used (a) for in vitro sensitization to TNP-self and (b) as a source of radioresistant helper cells for augmenting the TNP-self cytotoxic T lymphocyte (CTL) response generated by normal syngeneic spleen cells. Although spleen cells from unprimed mice from these two strains exhibited a comparable CTL response in a primary culture, a strong difference was observed in a secondary CTL response after in vivo priming. CTL activities generated in the secondary culture were much stronger in C3H/He than in B10.BR strains. This difference in the magnitude of secondary CTL responses was paralleled by generation of strong and weak helper cell activity in C3H/He and B10.BR, respectively. No detectable difference was observed between the two H-2k strains in the lysability of target cells and ability of stimulating cells to activate the primed unirradiated cells and radioresistant helper cells. This genetic difference detected in the H-2k haplotype was also demonstrated in the H-2b haplotype, by using C3H.SW and C57BL/10 mice which bear non-H-2 background genes corresponding to C3H/He and B10.BR mice, respectively. These results indicate the existence of a control mechanism influenced by non-H-2 genes, in addition to the established H-2-linked gene control.