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 (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.
Kedzierska
Katherine
K
Department of Microbiology and Immunology, University of Melbourne, Parkville, Melbourne, VIC, Australia. kkedz@unimelb.edu.au
Valkenburg
Sophie A
SA
Guillonneau
Carole
C
Hubert
Francois-Xavier
FX
Cukalac
Tania
T
Curtis
Joan M
JM
Stambas
John
J
Scott
Hamish S
HS
Kedzierski
Lukasz
L
Venturi
Vanessa
V
Davenport
Miles P
MP
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009975:Orthomyxoviridae / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017634:Self Tolerance / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology*; D000096927:AIRE Protein
D018984:Epitopes, T-Lymphocyte; D011948:Receptors, Antigen, T-Cell; D014157:Transcription Factors; D000096927:AIRE Protein