Involvement of both T cell receptor V<inf>α</inf> and V<inf>β</inf> variable region domains and α chain junctional region in viral antigen recognition

Abstract

We have studied the lymphocytic choriomeningitis virus (LCMV)‐specific cytotoxic T cell response in transgenic mice expressing either the T cell receptor (TcR) α (Vα2/JαTA31) or the corresponding TcR β (Vβ8.1/Dβ/Jβ2.4) chain originally isolated from the LCMV glyconrotein specific (residues 32–42), H‐2Db‐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 α or β chain can randomly pair with different Vβ or Vα chains without any obvious bias. However, upon infection with LCMV, reactive cytotoxic T lymphocytes (CTL) from P14 β‐transgenic mice were predominantly Vα2+ whereas CTL from P14 α‐transgenic mice preferentially expressed Vβ8.1 and unexpectedly also Vβ8.3 (but not Vβ8.2). Correspondingly the LCMV‐specific CTL response in both α and β 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 VJα and a more diverse VDJβ junctional region. This report demonstrates that the antigen specificity of the studied TcR depends on the specific combination of both TcR α and β chains which implies that amino acids located in the TcR Vα and Vβ segments as well as in the junctional region are involved in binding of the viral antigenic fragment. Copyright © 1991 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim