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 V alpha (V alpha 12.1, 14.1, 22) and two predominant J alpha segments. beta-chain variable-region usage was also conserved, with V beta 7 being used by five clones despite contributing less than 2% of peripheral blood lymphocyte V beta 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.
Institute of Molecular Medicine, John Radcliffe Hospital, Oxford.
P
P
Bowness
P A
PA
Moss
S
S
Rowland-Jones
J I
JI
Bell
A J
AJ
McMichael
D000595:Amino Acid Sequence; D000956:Antigens, Viral / Q000276:immunology*; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor / Q000235:genetics; D015796:HLA-B27 Antigen / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D009980:Influenza A virus / Q000276:immunology*; D008969:Molecular Sequence Data; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D013167:Spondylitis, Ankylosing / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014758:Viral Core Proteins / Q000276:immunology*
D000956:Antigens, Viral; D015796:HLA-B27 Antigen; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014758:Viral Core Proteins