Regulation of CD8+ T cell development by thymus-specific proteasomes.
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.
Murata
Shigeo
S
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
Sasaki
Katsuhiro
K
Kishimoto
Toshihiko
T
Niwa
Shin-Ichiro
S
Hayashi
Hidemi
H
Takahama
Yousuke
Y
Tanaka
Keiji
K
D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D020134:Catalytic Domain; D004847:Epithelial Cells / Q000201:enzymology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D006801:Humans; D038041:Lymphopoiesis; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology* / Q000201:enzymology* / Q000276:immunology
D001324:Autoantigens; D015395:Histocompatibility Antigens Class I; D010455:Peptides; D049452:Green Fluorescent Proteins; C520308:PSMB11 protein, human; D046988:Proteasome Endopeptidase Complex; C520309:proteasome subunit beta5t, mouse