Somatic Variation of Antigen-Recognition Specificity in H-2^b-TNP-Specific Cytotoxic T-Cell Clones

Abstract

The molecular mechanisms involved in MHC-restricted antigen recognition by T cells are incompletely understood. For example, the strikingly precise ability of certain T-cell clones to distinguish very similar antigens (Hurwitz et al. 1984) is in apparent contrast to the seemingly degenerate specificity of the virgin T-cell repertoire (Eichmann et al. 1983; Fey et al. 1984). We have therefore considered the possibility that antigen-induced proliferation leads to further somatic diversification of the virgin T-cell pool with subsequent selection of variants with increasingly better antigen recognition properties. We present here results from two experimental systems: (a) We determined the kinetics of the appearance of somatic variants in a long-term CTL clone, cultured with and without its antigen, during short-term exponential growth and (b) we analyzed the changes in the pattern of cross-reactivity in a collection of 42 H-2^b-restricted TNP-specific CTL clones over a period of several months. The data presented here suggest that (a) the antigen recognition structures of in vitro established cloned CTL lines may undergo continous rapid somatic variation and (b) the selective pressure of antigen stimulation leads to maintenance and/or improvement of the recognition specify of the CTL clones for the selecting antigen.