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Nat Immunol. 2015 Oct;16(10):1069-76. doi: 10.1038/ni.3237. Epub 2015 Aug 24.

TCR affinity for thymoproteasome-dependent positively selecting peptides conditions antigen responsiveness in CD8(+) T cells.

Author information

1
Division of Experimental Immunology, Institute for Genome Research, University of Tokushima, Tokushima, Japan.
2
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
3
Center for Immunology, Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USA.
4
Department of Immunology, Graduate School of Medicine, Nagoya University, Nagoya, Japan.
5
Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan.
6
Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.

Abstract

In the thymus, low-affinity T cell antigen receptor (TCR) engagement facilitates positive selection of a useful T cell repertoire. Here we report that TCR responsiveness of mature CD8(+) T cells is fine tuned by their affinity for positively selecting peptides in the thymus and that optimal TCR responsiveness requires positive selection on major histocompatibility complex class I-associated peptides produced by the thymoproteasome, which is specifically expressed in the thymic cortical epithelium. Thymoproteasome-independent positive selection of monoclonal CD8(+) T cells results in aberrant TCR responsiveness, homeostatic maintenance and immune responses to infection. These results demonstrate a novel aspect of positive selection, in which TCR affinity for positively selecting peptides produced by thymic epithelium determines the subsequent antigen responsiveness of mature CD8(+) T cells in the periphery.

PMID:
26301566
PMCID:
PMC4810782
DOI:
10.1038/ni.3237
[Indexed for MEDLINE]
Free PMC Article

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