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International Immunology, Vol. 13, No. 11, 1383-1390, November 2001
© 2001 Japanese Society for Immunology

Functional differences between influenza A-specific cytotoxic T lymphocyte clones expressing dominant and subdominant TCR

Thomas M. Lawson, Stephen Man, Eddy C. Y. Wang, Sheila Williams, Nicholas Amos, Geraldine M. Gillespie1, Paul A. Moss2 and Leszek K. Borysiewicz

Department of Medicine, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, UK
1 Institute of Molecular Medicine, Oxford OX3 9DU, UK
2 Department of Haematology, University of Birmingham, Birmingham B15 2TH, UK

Correspondence to: T. M. Lawson

We have shown that the dominance of CD8+ T cells expressing TCR Vß17 in the adult HLA-A*0201-restricted influenza A/M158–66-specific response is acquired following first antigen exposure. Despite the acquired dominance of Vß17+ cells, subdominant M158–66-specific clones expressing non-Vß17+ TCR persist in all individuals. To determine whether the affinity of the expressed TCR for the HLA-A*0201/M158–66 complex could influence functional properties, M158–66-specific clones expressing subdominant (non-Vß17+) TCR were compared to cytotoxic T lymphocyte (CTL) clones expressing dominant (Vß17+) TCR. The Vß17+ CTL required up to 10,000-fold lower amounts of M1 peptide to mediate lysis compared to CTL clones expressing other Vß gene segments. All Vß17+ CTL clones tested bound HLA-A*0201/M158–66 tetramer, but two of three CTL clones expressing other TCR did not bind tetramer. The inability of non-Vß17+ 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 Vß17+ CTL which dominate the HLA-A*0201-restricted CTL response against influenza A are not functionally distinct from subdominant non-Vß17+ CTL. The dominance of Vß17+ CTL is likely to result from a competitive advantage due to superior CTL avidity for the HLA-A*0201/M158–66 complex.

Keywords: cytotoxic T lymphocyte, infectious immunity virus, human, repertoire development, TCR

Transmitting editor: E. Simpson


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