Diversity and clonotypic composition of influenza-specific CD8+ TCR repertoires remain unaltered in the absence of Aire
✍ Scribed by 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
- Publisher
- John Wiley and Sons
- Year
- 2010
- Tongue
- English
- Weight
- 381 KB
- Volume
- 40
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
TCR repertoire diversity is important for the protective efficacy of CD8 1 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 1 CD8 1 ) and diverse (D b PA 224 1 CD8 1 , K d NP 147 1 CD8 1 ) 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 1 CD8 1 , D b PA 224 1 CD8 1 and K d NP 147 1 CD8 1 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.