The TCR's sensitivity to self peptide-MHC dictates the ability of naive CD8+ T cells to respond to foreign antigens

Fulton, Ross B; Hamilton, Sara E; Xing, Yan; Best, J Adam; Goldrath, Ananda W; Hogquist, Kristin A; Jameson, Stephen C
January 2015
Nature Immunology;Jan2015, Vol. 16 Issue 1, p107
Academic Journal
The strength with which complexes of self peptide and major histocompatibility complex (MHC) proteins are recognized by the T cell antigen receptor (TCR) dictates the homeostasis of naive CD8+ T cells, but its effect on reactivity to foreign antigens is controversial. As expression of the negative regulator CD5 correlates with self-recognition, we studied CD5lo and CD5hi naive CD8+ T cells. Gene-expression characteristics suggested CD5hi cells were better poised for reactivity and differentiation than were CD5lo cells, and we found that the CD5hi pool also exhibited more efficient clonal recruitment and expansion, as well as enhanced reactivity to inflammatory cues, during the recognition of foreign antigen. However, the recognition of complexes of foreign peptide and MHC was similar for both subsets. Thus, CD8+ T cells with higher self-reactivity dominate the immune response to foreign antigens, with implications for T cell repertoire diversity and autoimmunity.


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