Thymoproteasome Shapes Immunocompetent Repertoire of CD8+ T Cells

Takeshi Nitta, Shigeo Murata, Katsuhiro Sasaki, Hideki Fujii, Adiratna Mat Ripen, Naozumi Ishimaru, Shigeo Koyasu, Keiji Tanaka, Yousuke Takahama

Research output: Contribution to journalArticlepeer-review

158 Citations (Scopus)

Abstract

How self-peptides displayed in the thymus contribute to the development of immunocompetent and self-protective T cells is largely unknown. In contrast, the role of thymic self-peptides in eliminating self-reactive T cells and thereby preventing autoimmunity is well established. A type of proteasome, termed thymoproteasome, is specifically expressed by thymic cortical epithelial cells (cTECs) and is required for the generation of optimal cellularity of CD8+ T cells. Here, we show that cTECs displayed thymoproteasome-specific peptide-MHC class I complexes essential for the positive selection of major and diverse repertoire of MHC class I-restricted T cells. CD8+ T cells generated in the absence of thymoproteasomes displayed a markedly altered T cell receptor repertoire that was defective in both allogeneic and antiviral responses. These results demonstrate that thymoproteasome-dependent self-peptide production is required for the development of an immunocompetent repertoire of CD8+ T cells.

Original languageEnglish
Pages (from-to)29-40
Number of pages12
JournalImmunity
Volume32
Issue number1
DOIs
Publication statusPublished - 2010 Jan 29

Keywords

  • CELLIMMUNO
  • MOLIMMUNO

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Fingerprint

Dive into the research topics of 'Thymoproteasome Shapes Immunocompetent Repertoire of CD8+ T Cells'. Together they form a unique fingerprint.

Cite this