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

Ross B. Fulton, Sara E Hamilton Hart, Yan Xing, J. Adam Best, Ananda W. Goldrath, Kristin A Hogquist, Stephen C Jameson

Research output: Contribution to journalArticlepeer-review

147 Scopus citations

Abstract

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 CD5hinaive CD8+ T cells. Gene-expression characteristics suggested CD5 hi 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.

Original languageEnglish (US)
Pages (from-to)107-117
Number of pages11
JournalNature immunology
Volume16
Issue number1
DOIs
StatePublished - Dec 18 2015

Bibliographical note

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© 2015 Nature America, Inc.

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