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

Journal article

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: Lawson, T; Man, S; Wang, E; Williams, S; Amos, N

• Publication status: Published
• Journal: International immunology
• Volume: 13
• Issue: 11
• Pages: 1383-1390
• Publication date: 2001-11-01
• DOI: 10.1093/intimm/13.11.1383
• EISSN: 1460-2377
• ISSN: 0953-8178
• Language: English
• Keywords: Influenza A virus; Adult; T-Lymphocytes, Cytotoxic; Receptors, Antigen, T-Cell, alpha-beta; Viral Matrix Proteins; HLA-A Antigens; Clone Cells; Humans; Peptides