Cross-reactivity patterns of vaccinia-specific cytotoxic T lymphocytes from H-2Kb mutants.

Limit-dilution cultures were used to select vaccinia-immune T-cell populations from bm1 and bm3 mutant mice that were not lytic for virus-infected targets expressing the Kb and Db MHC glycoprotein. Approximately 30% of virus-immune CTL were restricted in each case to Kbm1 and Kbm3, rather than to Db. Evidence of extensive cross-reactivity was found for these virus-immune CTL. Bm3 and bm11 mice sharing one amino acid mutation from wild-type but differing by a second mutation seen only in bm3 are the most cross-reactive pair in their presentation of vaccinia. The bm1 and bm10 pair with dissimilar mutations from wild-type affecting the same CNBr fragment are also largely cross-reactive. However, 30% cross-reactivity is also found for bm1 and bm3, which differ in separate CNBr fragments. That mutants expressing amino acid substitutions in the same region of the peptide tend to show more evidence of cross-reactivity does not necessarily mean the T cells see linear arrays of amino acids on the MHC glycoprotein. For instance, Kbm1 and Kbm10 differ for three amino acids, but bm1 T cells are highly lytic for bm10 virus-infected targets. However, there is no cross-reactivity for Kbm1 and Kb, which differ at only two amino acids. The key to further understanding may rest with defining the nature of the conformational differences among the Kbm1, Kbm10, and Kb glycoproteins.