CONSERVATION OF T-CELL RECEPTOR USAGE BY HLA B27-RESTRICTED INFLUENZA-SPECIFIC CYTOTOXIC T-LYMPHOCYTES SUGGESTS A GENERAL PATTERN FOR ANTIGEN-SPECIFIC MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I-RESTRICTED RESPONSES

Eight HLA B27-restricted influenza A virus nucleoprotein 383-391-specific cytotoxic T lymphocyte (CTL) clones were obtained from three unrelated donors following natural infection. T cell receptor (TcR) usage was studied using the ''anchored'' polymerase chain reaction. TcR alpha-chain usage was restricted with three predominant Valpha (Valpha 12.1, 14.1, 22) and two predominant Jalpha segments. beta-chain variable-region usage was also conserved, with Vbeta7 being used by five clones despite contributing less than 2% of peripheral blood lymphocyte Vbeta sequences of one individual studied. The TcR beta-chain junctional region was highly conserved even between CTL clones from unrelated individuals, with a negatively charged amino acid, contributed to by N-region addition, encoded at position 97 in all but two clones. This study shows that peptide-specific HLA B27-restricted CTL following influenza virus infection use very similar TcR and, when considered with previous studies, suggests a pattern of TcR conservation for major histocompatibility complex class I-restricted responses. No difference in TcR usage was detected between one healthy donor and two with HLA B27-associated arthritis.