Influence of H-2-linked genes on T cell proliferative and cytolytic responses to peptides of Sendai viral proteins

Spleen cells from a number of H-2 congenic mice were tested for their proliferative and/or cytolytic responses to partially purified products from CNBr cleavage of Sendai virus. In response to in vitro stimulation of Sendai-primed spleen cells with virus-infected cells, Sendai virus-specific cytolytic T lymphocytes restricted to H-2K(b), K(d), K(k), K(a), and D(d) were generated. Of these, H-2K(b)- and K(d)-, but not H-2K(k)-, K(a)-, and D(d)-, restricted cytolytic T cells were generated after stimulation with partially purified Sendai peptides. H-2D(d)-restmicted, virus-specific cytotoxicity was generated in response to unseparated products from CNBr cleavage of Sendai virus. Thus, the pool of partially purified peptides contains some but not all of the antigenic determinants that can stimulate a cytolytic response. These results suggest that each determinant on Sendai viral proteins may stimulate cytolytic T lymphocytes restricted to only a subset of the H-2K and D alleles which can be recognized by the sum of cytolytic T cells generated in response to all of the antigenic determinants on Sendai viral proteins. Thus, H-2K and D genes function as immune response genes regulating the cytolytic response to partially purified peptides and, by extension, possibly to individual antigenic determinants on Sendai viral proteins. Also, spleen cells from three mice differing only in the H-2I-S regions show differences in their proliferative responses to Sendai antigens. Only spleen cells from mice with the k haplotype in IA-IJ proliferate in response to partially purified peptides, whereas spleen cells from all three mice proliferate when virus is added to the cultures. These proliferating cells are sensitive to treatment with anti-Thy-1.2 and C, suggesting that immune response genes regulating T cell proliferative responses to individual viral determinants may also exist.