Regulation of CD8+ T cell development by thymus-specific proteasomes

Shigeo Murata; Katsuhiro Sasaki; Toshihiko Kishimoto; Shin-Ichiro Niwa; Hidemi Hayashi; Yousuke Takahama; Keiji Tanaka

doi:10.1126/science.1141915

Regulation of CD8+ T cell development by thymus-specific proteasomes

Science. 2007 Jun 1;316(5829):1349-53. doi: 10.1126/science.1141915.

Authors

Shigeo Murata¹, Katsuhiro Sasaki, Toshihiko Kishimoto, Shin-Ichiro Niwa, Hidemi Hayashi, Yousuke Takahama, Keiji Tanaka

Affiliation

¹ Laboratory of Frontier Science, Core Technology and Research Center, Tokyo Metropolitan Institute of Medical Science, Bunkyo-ku, Tokyo 113-8613, Japan. smurata@rinshoken.or.jp

PMID: 17540904
DOI: 10.1126/science.1141915

Abstract

Proteasomes are responsible for generating peptides presented by the class I major histocompatibility complex (MHC) molecules of the immune system. Here, we report the identification of a previously unrecognized catalytic subunit called beta5t. beta5t is expressed exclusively in cortical thymic epithelial cells, which are responsible for the positive selection of developing thymocytes. Although the chymotrypsin-like activity of proteasomes is considered to be important for the production of peptides with high affinities for MHC class I clefts, incorporation of beta5t into proteasomes in place of beta5 or beta5i selectively reduces this activity. We also found that beta5t-deficient mice displayed defective development of CD8(+) T cells in the thymus. Our results suggest a key role for beta5t in generating the MHC class I-restricted CD8(+) T cell repertoire during thymic selection.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Animals
Autoantigens / immunology
Autoantigens / metabolism
CD4-Positive T-Lymphocytes / cytology
CD4-Positive T-Lymphocytes / immunology
CD8-Positive T-Lymphocytes / cytology
CD8-Positive T-Lymphocytes / immunology*
Catalytic Domain
Epithelial Cells / enzymology
Green Fluorescent Proteins / genetics
Green Fluorescent Proteins / metabolism
Histocompatibility Antigens Class I / immunology
Histocompatibility Antigens Class I / metabolism
Humans
Lymphopoiesis
Molecular Sequence Data
Peptides / chemistry
Peptides / metabolism
Proteasome Endopeptidase Complex / chemistry
Proteasome Endopeptidase Complex / genetics
Proteasome Endopeptidase Complex / metabolism*
Spleen / cytology
Spleen / immunology
T-Lymphocyte Subsets / cytology
T-Lymphocyte Subsets / immunology
Thymus Gland / cytology*
Thymus Gland / enzymology*
Thymus Gland / immunology

Substances

Autoantigens
Histocompatibility Antigens Class I
Peptides
Green Fluorescent Proteins
PSMB11 protein, human
Proteasome Endopeptidase Complex
proteasome subunit beta5t, mouse

Associated data

GENBANK/AB299436
GENBANK/AB299437