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

Kedzierska, K; Valkenburg, SA; Guillonneau, C; Hubert, FX; Cukalac, T; Curtis, JM; Stambas, J; Scott, HS; Kedzierski, L; Venturi, V; Davenport, MP

Author(s): Kedzierska, K; Valkenburg, SA; Guillonneau, C; Hubert, FX; Cukalac, T; Curtis, JM; Stambas, J; Scott, HS; Kedzierski, L; Venturi, V; Davenport, MP;
Details: Publication Year 2010-03,Volume 40,Issue #3,Page 849-858
Journal Title: EUROPEAN JOURNAL OF IMMUNOLOGY
Publication Type: Journal Article
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.
Publisher: WILEY-BLACKWELL
Keywords: T-CELL RESPONSES; VIRUS NUCLEOPROTEIN EPITOPE; THYMIC EPITHELIAL-CELLS; DEFICIENT MICE; RECEPTOR RECOGNITION; STRUCTURAL BASIS; LYMPH-NODE; IN-VIVO; EXPRESSION; GENE
Publisher's Version: https://doi.org/10.1002/eji.200939918
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2010-03-01 12:00:00