Thymoproteasome shapes immunocompetent repertoire of CD8+ T cells.
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.
Nitta
Takeshi
T
Division of Experimental Immunology, Institute for Genome Research, University of Tokushima, Tokushima 770-8503, Japan.
Murata
Shigeo
S
Sasaki
Katsuhiro
K
Fujii
Hideki
H
Ripen
Adiratna Mat
AM
Ishimaru
Naozumi
N
Koyasu
Shigeo
S
Tanaka
Keiji
K
Takahama
Yousuke
Y
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology*; D004847:Epithelial Cells / Q000276:immunology* / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D046988:Proteasome Endopeptidase Complex / Q000276:immunology*; D017634:Self Tolerance / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D015395:Histocompatibility Antigens Class I; D046988:Proteasome Endopeptidase Complex