INVOLVEMENT OF BOTH T-CELL RECEPTOR V-ALPHA AND V-BETA VARIABLE REGION DOMAINS AND ALPHA-CHAIN JUNCTIONAL REGION IN VIRAL-ANTIGEN RECOGNITION

We have studied the lymphocytic choriomeningitis virus (LCMV)-specific cytotoxic T cell response in transgenic mice expressing either the T cell receptor (TcR) alpha (V-alpha-2/J-alpha-TA31) or the corresponding TcR beta (V-beta-8.1/D-beta/J-beta-2.4) chain originally isolated from the LCMV glycoprotein specific (residues 32-42), H-2D(b)-restricted T cell clone P14. The expression of single transgenic TcR chains did not influence the corresponding endogenous TcR V gene usage in unstimulated T cells indicating that one particular TcR-alpha or beta-chain can randomly pair with different V-beta or V-alpha chains without any obvious bias. However, upon infection with LCMV, reactive cytotoxic T lymphocytes (CTL) from P14 beta-transgenic mice were predominantly V-alpha-2+ whereas CTL from P14 alpha-transgenic mice preferentially expressed V-beta-8.1 and unexpectedly also V-beta-8.3 (but not V-beta-8.2). Correspondingly, the LCMV-specific CTL response in both alpha and beta TcR-transgenic mice was strongly biased to the original P14 T cell epitope (LCMV glycoprotein residues 32-42). Sequence analysis of a large panel of LCMV-reactive "half-transgenic" TcR from P14 single receptor chain-transgenic mice revealed a highly conserved VJ-alpha and a more diverse VDJ-beta-junctional region. This report demonstrates that the antigen specificity of the studied TcR depends on the specific combination of both TcR-alpha and beta-chains which implies that amino acids located in the TcR V-alpha and V-beta segments as well as in the junctional region are involved in binding of the viral antigenic fragment.