Elimination of T-cell-receptor beta-chain diversity in transgenic mice restricts antigen-specific but not alloreactive responses.

The contribution of T-cell-receptor beta-chain diversity to the T-cell antigen-specific repertoire was investigated using single-chain T-cell-receptor transgenic mice. Animals that express the rearranged beta-chain gene from a T hybridoma with specificity for a hen egg lysozyme peptide, designated HEL (85-96) were analysed for their ability to respond to a panel of diverse antigens. Transgenic mice exhibited a significantly elevated response to HEL (85-96) which was shown to be due to an increased frequency of HEL (85-96)-specific T-cell progenitors. This increased frequency of specific progenitors resulted in the ability of transgenic mice to respond to the peptide in the absence of antigen priming. Conversely, transgenic mice failed to respond to any other antigen tested. Furthermore, this apparent deficiency was associated with a significant decrease in the frequency of antigen-specific T-cell progenitors in transgenic mice. Surprisingly, the ability to launch an alloresponse was unaffected by the exclusive expression of the transgene-derived beta-chain. These results indicate that beta-chain diversity is crucial for the ability of the T-cell population to elicit a rapid and robust response to the profusion of different antigen/major histocompatibility complex (MHC) ligands potentially encountered by an individual. Furthermore, these results suggest a lesser role for beta-chain diversity in contributing to allorecognition, and support a model in which the direct recognition of peptide-mediated conformational MHC forms is the major contributor to the alloreactive response exhibited by the majority of T cells.