title: Functional differences between influenza A-specific cytotoxic T lymphocyte clones expressing dominant and subdominant TCR.
abstract: We have shown that the dominance of CD8+ T cells expressing TCR Vbeta17 in the adult HLA-A*0201-restricted influenza A/M1(58-66)-specific response is acquired following first antigen exposure. Despite the acquired dominance of Vbeta17+ cells, subdominant M1(58-66)-specific clones expressing non-Vbeta17+ TCR persist in all individuals. To determine whether the affinity of the expressed TCR for the HLA-A*0201/M1(58-66) complex could influence functional properties, M1(58-66)-specific clones expressing subdominant (non-Vbeta17+) TCR were compared to cytotoxic T lymphocyte (CTL) clones expressing dominant (Vbeta17+) TCR. The Vbeta17+ CTL required up to 10,000-fold lower amounts of M1 peptide to mediate lysis compared to CTL clones expressing other Vbeta gene segments. All Vbeta17+ CTL clones tested bound HLA-A*0201/M1(58-66) tetramer, but two of three CTL clones expressing other TCR did not bind tetramer. The inability of non-Vbeta17+ CTL to bind tetramer did not correlate with phenotype, CD8 dependence or with cytokine production profiles. This suggests a limitation for the use of tetramers in examining subdominant T cell responses. Together these findings suggest that Vbeta17+ CTL which dominate the HLA-A*0201-restricted CTL response against influenza A are not functionally distinct from subdominant non-Vbeta17+ CTL. The dominance of Vbeta17+ CTL is likely to result from a competitive advantage due to superior CTL avidity for the HLA-A*0201/M1(58-66) complex.
authors.affiliation: Department of Medicine, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, UK.
authors.forename: T M
authors.initials: TM
authors.lastname: Lawson
authors.forename: S
authors.initials: S
authors.lastname: Man
authors.forename: E C
authors.initials: EC
authors.lastname: Wang
authors.forename: S
authors.initials: S
authors.lastname: Williams
authors.forename: N
authors.initials: N
authors.lastname: Amos
authors.forename: G M
authors.initials: GM
authors.lastname: Gillespie
authors.forename: P A
authors.initials: PA
authors.lastname: Moss
authors.forename: L K
authors.initials: LK
authors.lastname: Borysiewicz
mesh_terms: D000328:Adult; D002999:Clone Cells; D015234:HLA-A Antigens / Q000378:metabolism; D006801:Humans; D009980:Influenza A virus / Q000276:immunology*; D010455:Peptides / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D014763:Viral Matrix Proteins / Q000276:immunology
chemical_list: D015234:HLA-A Antigens; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014763:Viral Matrix Proteins