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-cel l-receptor transgenic mice. Animals that express the rearranged beta-c hain gene from a T hybridoma with specificity for a hen egg lysozyme p eptide, designated HEL(85-96) were analysed for their ability to respo nd to a panel of diverse antigens. Transgenic mice exhibited a signifi cantly 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 i ncreased frequency of specific progenitors resulted in the ability of transgenic mice to respond to the peptide in the absence of antigen pr iming. Conversely, transgenic mice failed to respond to any other anti gen tested. Furthermore, this apparent deficiency was associated with a significant decrease in the frequency of antigen-specific T-cell pro genitors in transgenic mice. Surprisingly, the ability to launch an al loresponse 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 histoc ompatibility complex (MHC) ligands potentially encountered by an indiv idual. 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 fo rms is the major contributor to the alloreactive response exhibited by the majority of T cells.