PMID- 20045355 OWN - NLM STAT- MEDLINE DCOM- 20100323 LR - 20100215 IS - 1097-4180 (Electronic) IS - 1074-7613 (Linking) VI - 32 IP - 1 DP - 2010 Jan 29 TI - Thymoproteasome shapes immunocompetent repertoire of CD8+ T cells. PG - 29-40 LID - 10.1016/j.immuni.2009.10.009 [doi] AB - 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. CI - Copyright 2010 Elsevier Inc. All rights reserved. FAU - Nitta, Takeshi AU - Nitta T AD - Division of Experimental Immunology, Institute for Genome Research, University of Tokushima, Tokushima 770-8503, Japan. FAU - Murata, Shigeo AU - Murata S FAU - Sasaki, Katsuhiro AU - Sasaki K FAU - Fujii, Hideki AU - Fujii H FAU - Ripen, Adiratna Mat AU - Ripen AM FAU - Ishimaru, Naozumi AU - Ishimaru N FAU - Koyasu, Shigeo AU - Koyasu S FAU - Tanaka, Keiji AU - Tanaka K FAU - Takahama, Yousuke AU - Takahama Y LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20091231 PL - United States TA - Immunity JT - Immunity JID - 9432918 RN - 0 (Histocompatibility Antigens Class I) RN - EC 3.4.25.1 (Proteasome Endopeptidase Complex) SB - IM MH - Animals MH - CD8-Positive T-Lymphocytes/cytology/*immunology/metabolism MH - Cell Differentiation/*immunology MH - Epithelial Cells/*immunology/metabolism MH - Histocompatibility Antigens Class I/immunology MH - Lymphocyte Activation/immunology MH - Mice MH - Mice, Knockout MH - Proteasome Endopeptidase Complex/*immunology MH - Self Tolerance/immunology MH - T-Lymphocyte Subsets/cytology/*immunology/metabolism MH - Thymus Gland/cytology/immunology/metabolism EDAT- 2010/01/05 06:00 MHDA- 2010/03/24 06:00 CRDT- 2010/01/05 06:00 PHST- 2009/06/16 00:00 [received] PHST- 2009/10/03 00:00 [revised] PHST- 2009/10/14 00:00 [accepted] PHST- 2010/01/05 06:00 [entrez] PHST- 2010/01/05 06:00 [pubmed] PHST- 2010/03/24 06:00 [medline] AID - S1074-7613(09)00543-3 [pii] AID - 10.1016/j.immuni.2009.10.009 [doi] PST - ppublish SO - Immunity. 2010 Jan 29;32(1):29-40. doi: 10.1016/j.immuni.2009.10.009. Epub 2009 Dec 31.