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 journalArticle

25 Citations (Scopus)

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

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T-Cell Antigen Receptor
T-Lymphocytes
Antigens
Peptides
Thymus Gland
Epithelium
Major Histocompatibility Complex
Maintenance
Infection

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TCR affinity for thymoproteasome-dependent positively selecting peptides conditions antigen responsiveness in CD8+ T cells. / Takada, Kensuke; Van Laethem, Francois; Xing, Yan; Akane, Kazuyuki; Suzuki, Haruhiko; Murata, Shigeo; Tanaka, Keiji; Jameson, Stephen C.; Singer, Alfred; Takahama, Yousuke.

In: Nature immunology, Vol. 16, No. 10, 18.09.2015, p. 1069-1076.

Research output: Contribution to journalArticle

Takada, K, Van Laethem, F, Xing, Y, Akane, K, Suzuki, H, Murata, S, Tanaka, K, Jameson, SC, Singer, A & Takahama, Y 2015, 'TCR affinity for thymoproteasome-dependent positively selecting peptides conditions antigen responsiveness in CD8+ T cells', Nature immunology, vol. 16, no. 10, pp. 1069-1076. https://doi.org/10.1038/ni.3237
Takada, Kensuke ; Van Laethem, Francois ; Xing, Yan ; Akane, Kazuyuki ; Suzuki, Haruhiko ; Murata, Shigeo ; Tanaka, Keiji ; Jameson, Stephen C. ; Singer, Alfred ; Takahama, Yousuke. / TCR affinity for thymoproteasome-dependent positively selecting peptides conditions antigen responsiveness in CD8+ T cells. In: Nature immunology. 2015 ; Vol. 16, No. 10. pp. 1069-1076.
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