CD8 T-cell ability to exert immunodomination correlates with T-cell receptor: epitope association rate.
When presented alone, H7 a and HY antigens elicit CD8 T-cell responses of similar amplitude, but H7 a totally abrogates the response to HY when both antigens are presented on the same antigen-presenting cell. We found that H7a- and HY-specific T-cell precursors had similar frequencies in nonimmune mice and expressed similar levels of CD5. The H7a -specific CD8 T-cell repertoire harvested at the time of primary response showed highly restricted T-cell receptor (TCR) diversity. Furthermore, T cells specific for H7a and HY expressed equivalent levels of CD8 and TCR and displayed similar tetramer decay rates. The key difference was that anti-H7a T cells exhibited a much more rapid TCR:epitope on-rate than anti-HY T cells. Coupled with evidence that primed CD8 T cells limit the duration of antigen presentation by killing or inactivating antigen-presenting cells, our data support a novel and simple model for immunodomination: the main feature of T cells that exert immunodomination is that, compared with other T cells, they are functionally primed after a shorter duration of antigen presentation.
Roy-Proulx
Guillaume
G
Institute of Research in Immunology and Cancer, University of Montreal, Montreal, Quebec, Canada.
Baron
Chantal
C
Perreault
Claude
C
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D006182:H-Y Antigen / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D006182:H-Y Antigen; D011948:Receptors, Antigen, T-Cell