Journal
NATURE IMMUNOLOGY
Volume 16, Issue 10, Pages 1069-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.3237
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Funding
- MEXT-JSPS [24111004, 23249025, 24790475, 26460576]
- Naito Foundation
- Takeda Science Foundation
- Uehara Memorial Foundation
- Grants-in-Aid for Scientific Research [23249025, 24790475, 24111001, 24111004, 26000014] Funding Source: KAKEN
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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.
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