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

被引：151
作者：
Fulton, Ross B. [1 ]
Hamilton, Sara E. [1 ]
Xing, Yan [1 ]
Best, J. Adam [2 ]
Goldrath, Ananda W. [2 ]
Hogquist, Kristin A. [1 ]
Jameson, Stephen C. [1 ]
机构：
[1] Univ Minnesota, Sch Med, Ctr Immunol, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA
[2] Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA
来源：
NATURE IMMUNOLOGY | 2015年 / 16卷 / 01期
基金：
美国国家卫生研究院;
关键词：
MEMORY; EXPRESSION; EFFECTOR; SURVIVAL; DIFFERENTIATION; REPERTOIRE; AFFINITY; STRENGTH; SIGNALS; RESPONSIVENESS;
D O I：
10.1038/ni.3043
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
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 CD5(lo) and CD5(hi) naive CD8(+) T cells. Gene-expression characteristics suggested CD5(hi) cells were better poised for reactivity and differentiation than were CD5(lo) cells, and we found that the CD5(hi) 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.
引用
收藏
页码：107 / +
页数：13
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