Multiple cytolytic T-cell clones with distinct cross-reactivity patterns coexist in anti-self + hapten cell lines

Abstract

C57BL/10 T cells sensitized with TNBS-treated syngeneic cells and maintained in culture by repeated stimulations exhibit high cytolytic activity toward syngeneic TNBS-treated target cells with marked cross-reactivity on TNBS-treated target cells from mice of independent H-2 haplotypes (ten tested). The analysis of the reactivities of 48 T-cell clones derived by limiting dilution from such T-cell populations revealed three types of cytotoxic T-cell clones: (1) clones restricted by H-2Kb + TNP without cross-reaction on TNBS-treated or untreated target cells of other tested mouse haplotypes; (2) clones that lysed H-2b + TNP and also TNBS-treated target cells from not more than one, two or three different H-2 haplotypes; (3) clones that lysed untreated H-2k target cells. No T-cell clone was found to exhibit the wide pattern of cross-reactivity on any TNBS-treated mouse cell, characteristic of the original T-cell populations, indicating that these were composed of individual T-cell clones specific for TNP + private or for TNP + distinct "public" H-2 determinants. Correlation with described serological public H-2 specificities was possible for some cytotoxic T-cell clone reactivity, but not for others. The general pattern of T-cell reactivity as revealed by clonal analysis in this study, as well as in published work, includes cross-reactions between self H-2a + X and allogeneic H-2n + X, between self H-2a + X and unmodified allogeneic H-2n, or between allogeneic H-2n and allogeneic H-2m + X, and is consistent with the hypothesis that MHC-class restriction is the main rule in T-cell recognition.