Regulation of CD8+ T cell development by thymus-specific proteasomes - PubMed (original) (raw)

. 2007 Jun 1;316(5829):1349-53.

doi: 10.1126/science.1141915.

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

Shigeo Murata et al. Science. 2007.

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.

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