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 mechanismfor 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 (D bPA224+CD8+, KdNP 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, 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. © 2009 Wiley-VCH Verlag GmbH & Co. KGaA.