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

Kensuke Takada, Francois Van Laethem, Yan Xing, Kazuyuki Akane, Haruhiko Suzuki, Shigeo Murata, Keiji Tanaka, Stephen C. Jameson, Alfred Singer, Yousuke Takahama

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1069-1076
Number of pages8
JournalNature immunology
Volume16
Issue number10
DOIs
StatePublished - Sep 18 2015

Bibliographical note

Funding Information:
We thank H. Kosako, I. Ohigashi, M. Kozai and B. Kim for helpful discussion and reading the manuscript. This work was supported by grants from MEXT-JSPS (24111004 and 23249025 to Y.T. and 24790475 and 26460576 to K. Takada), Naito Foundation (to Y.T. and K. Takada), Takeda Science Foundation (to K. Takada), and Uehara Memorial Foundation (to K. Takada).

Publisher Copyright:
© 2015 Nature America, Inc. All rights reserved.

Fingerprint Dive into the research topics of 'TCR affinity for thymoproteasome-dependent positively selecting peptides conditions antigen responsiveness in CD8+ T cells'. Together they form a unique fingerprint.

Cite this