The immunoproteasome and thymoproteasome: functions, evolution and human disease

Abstract

The basic principle of adaptive immunity is to strictly discriminate between self and non-self, and a central challenge to overcome is the enormous variety of pathogens that might be encountered. In cell-mediated immunity, immunological discernment takes place at a molecular or cellular level. Central to both mechanisms of discernment is the generation of antigenic peptides associated with MHC class I molecules, which is achieved by a proteolytic complex called the proteasome. To adequately accomplish the discrimination between self and non-self that is essential for adaptive immunity and self-tolerance, two proteasome subtypes have evolved via gene duplication: the immunoproteasome and the thymoproteasome. In this Review, we describe various aspects of these immunity-dedicated proteasomes, from their discovery to recent findings.

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Fig. 1: Structures and diversity of the proteasome.
Fig. 2: Mechanisms of thymoproteasome-mediated positive selection.
Fig. 3: Evolution of adaptive immunity and proteasomes.

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Murata, S., Takahama, Y., Kasahara, M. et al. The immunoproteasome and thymoproteasome: functions, evolution and human disease. Nat Immunol 19, 923–931 (2018). https://doi.org/10.1038/s41590-018-0186-z

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