Fixing an irrelevant TCR alpha chain reveals the importance of TCR beta diversity for optimal TCR alpha beta pairing and function of virus-specific CD8+ T cells.

Abstract

TCR repertoire diversity can influence the efficacy of CD8(+) T-cell populations, with greater breadth eliciting better protection. We analyzed TCR beta diversity and functional capacity for influenza-specific CD8(+) T cells expressing a single TCR alpha chain. Mice (A7) transgenic for the H2K(b)OVA(257-264)-specific V alpha 2.7 TCR were challenged with influenza to determine how fixing this "irrelevant" TCR alpha affects the "public" and restricted D(b)NP(366) (+)CD8(+) versus the "private" and diverse D(b)PA(224) (+)CD8(+) responses. Though both D(b)NP(366) (+)CD8(+) and D(b)PA(224) (+)CD8(+) sets are generated in virus-primed A7 mice, the constrained D(b)NP(366) (+)CD8(+) population lacked the characteristic, public TCRV beta 8.3, and consequently was reduced in magnitude and pMHC-I avidity. For the more diverse D(b)PA(224) (+)CD8(+) T cells, this particular forcing led to a narrowing and higher TCR beta conservation of the dominant V beta 7, though the responses were of comparable magnitude to C57BL/6J controls. Interestingly, although both the TCR beta diversity and the cytokine profiles were reduced for the D(b)NP(366) (+)CD8(+) and D(b)PA(224) (+)CD8(+) sets in spleen, the latter measure of polyfunctionality was comparable for T cells recovered from the infected lungs of A7 and control mice. Even "sub-optimal" TCR alpha beta pairs can operate effectively when exposed in a milieu of high virus load. Thus, TCR beta diversity is important for optimal TCR alpha beta pairing and function when TCR alpha is limiting.

• Authors: Sophie A Valkenburg, E Bridie Day, Natasha G Swan, Hayley A Croom, Francis R Carbone, Peter C Doherty, Stephen J Turner, Katherine Kedzierska
• Journal: European journal of immunology (Eur J Immunol) Vol. 40 Issue 9 Pg. 2470-81 (Sep 2010) ISSN: 1521-4141 [Electronic] Germany
• PMID: 20690181 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• H-2 Antigens
• H-2Kb protein, mouse
• Histocompatibility Antigen H-2D
• Peptide Fragments
• Receptors, Antigen, T-Cell, alpha-beta
• Viral Core Proteins
• nucleoprotein (366-374), influenza virus
• Ovalbumin

Topics

• Animals
• CD8-Positive T-Lymphocytes (immunology, metabolism, pathology, virology)
• Cells, Cultured
• Cytokines (metabolism)
• Genes, T-Cell Receptor beta (genetics, immunology)
• Genetic Variation (immunology)
• H-2 Antigens (immunology, metabolism)
• Histocompatibility Antigen H-2D
• Influenza A virus (immunology, pathogenicity)
• Lung (immunology, pathology, virology)
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Orthomyxoviridae Infections (genetics, immunology, virology)
• Ovalbumin (immunology)
• Peptide Fragments (immunology)
• Protein Multimerization (immunology)
• Receptors, Antigen, T-Cell, alpha-beta (genetics, immunology, metabolism)
• Viral Core Proteins (immunology)