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Thymoproteasomes produce unique peptide motifs for positive selection of CD8(+) T cells.

Abstract：

: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_name

Nat Commun

journal_title

Nature communications

authors

Sasaki K,Takada K,Ohte Y,Kondo H,Sorimachi H,Tanaka K,Takahama Y,Murata S

doi

10.1038/ncomms8484

subject

Has Abstract

pub_date

2015-06-23 00:00:00

pages

7484

issn

2041-1723

pii

ncomms8484

journal_volume

6

pub_type

杂志文章

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