Diversity and clonotypic composition of influenza-specific CD8+ TCR repertoires remain unaltered in the absence of Aire
Kedzierska, Katherine, Valkenburg, Sophie A., Guillonneau, Carole, Hubert, Francois-Xavier, Cukalac, Tania, Curtis, Joan M., Stambas, John, Scott, Hamish S., Kedzierski, Lukasz, Venturi, Vanessa and Davenport, Miles P. 2010, Diversity and clonotypic composition of influenza-specific CD8+ TCR repertoires remain unaltered in the absence of Aire, European journal of immunology, vol. 40, no. 3, pp. 849-858.
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Diversity and clonotypic composition of influenza-specific CD8+ TCR repertoires remain unaltered in the absence of Aire
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 (DbNP366%+CD8+) and diverse (DbPA224%+CD8+, KdNP147%+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, DbNP366%+CD8+, DbPA224%+CD8+ and KdNP147%+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.