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ID 115643
Author
Sasaki, Katsuhiro The University of Tokyo|Kyoto University
Ohte, Yuki The University of Tokyo
Kondo, Hiroyuki University of Tokushima
Sorimachi, Hiroyuki Tokyo Metropolitan Institute of Medical Science
Tanaka, Keiji Tokyo Metropolitan Institute of Medical Science
Murata, Shigeo The University of Tokyo
Content Type
Journal Article
Description
Positive selection in the thymus provides low-affinity T-cell receptor (TCR) engagement to support the development of potentially useful self-major histocompatibility complex class I (MHC-I)-restricted T cells. Optimal positive selection of CD8+ T cells requires cortical thymic epithelial cells that express β5t-containing thymoproteasomes (tCPs). However, how tCPs govern positive selection is unclear. Here we show that the tCPs produce unique cleavage motifs in digested peptides and in MHC-I-associated peptides. Interestingly, MHC-I-associated peptides carrying these tCP-dependent motifs are enriched with low-affinity TCR ligands that efficiently induce the positive selection of functionally competent CD8+ T cells in antigen-specific TCR-transgenic models. These results suggest that tCPs contribute to the positive selection of CD8+ T cells by preferentially producing low-affinity TCR ligand peptides.
Journal Title
Nature Communications
ISSN
20411723
NCID
AA12645905
Publisher
Springer Nature
Volume
6
Start Page
7484
Published Date
2015-06-23
Rights
This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
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DOI (Published Version)
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FullText File
language
eng
TextVersion
Publisher
departments
Institute of Advanced Medical Sciences