Diversity and clonotypic composition of influenza-specific CD8+ TCR repertoires remain unaltered in the absence of Aire.

Abstract

TCR repertoire diversity is important for the protective efficacy of CD8(+) T cells, limiting viral escape and cross-reactivity between unrelated epitopes. The exact mechanism for selection of restricted versus diverse TCR repertoires is far from clear, although one thought is that the epitopes resembling self-peptides might select a limited array of TCR due to the deletion of autoreactive TCR. The molecule Aire promotes the expression of tissue-specific Ag on thymic medullary epithelial cells and the deletion of autoreactive cells, and in the absence of Aire autoreactive cells persist. However, the contribution of Aire-dependent peptides to the selection of the Ag-specific TCR repertoire remains unknown. In this study, we dissect restricted (D(b)NP(366)%(+)CD8(+)) and diverse (D(b)PA(224)%(+)CD8(+), K(d)NP(147)%(+)CD8(+)) TCR repertoires responding to three influenza-derived peptides in Aire-deficient mice on both B6 and BALB/c backgrounds. Our study shows that the number, qualitative characteristics and TCR repertoires of all influenza-specific, D(b)NP(366)%(+)CD8(+), D(b)PA(224)%(+)CD8(+) and K(d)NP(147)%(+)CD8(+) T cells are not significantly altered in the absence of Aire. This provides the first demonstration that the selection of an Ag-specific T-cell repertoire is not significantly perturbed in the absence of Aire.

• Authors: Katherine Kedzierska, Sophie A Valkenburg, Carole Guillonneau, Francois-Xavier Hubert, Tania Cukalac, Joan M Curtis, John Stambas, Hamish S Scott, Lukasz Kedzierski, Vanessa Venturi, Miles P Davenport
• Journal: European journal of immunology (Eur J Immunol) Vol. 40 Issue 3 Pg. 849-58 (Mar 2010) ISSN: 1521-4141 [Electronic] Germany
• PMID: 19950188 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• APECED protein
• Epitopes, T-Lymphocyte
• Receptors, Antigen, T-Cell
• Transcription Factors

Topics

• Animals
• CD8-Positive T-Lymphocytes (immunology)
• Epitopes, T-Lymphocyte (immunology)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Knockout
• Orthomyxoviridae (immunology)
• Orthomyxoviridae Infections (immunology)
• Receptors, Antigen, T-Cell (genetics, immunology)
• Reverse Transcriptase Polymerase Chain Reaction
• Self Tolerance (immunology)
• Transcription Factors (genetics, immunology)