Involvement of both T cell receptor Vα and Vβ variable region domains and α 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) 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.