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Generation of major histocompatibility complex class I antigens: functional interplay between proteasomes and TPPII

Nature Immunology volume 5, pages 661–669 (2004)Cite this article

Abstract

The proteasome is key in the cascade of proteolytic processing required for the generation of peptides presented at the cell surface to cytotoxic T lymphocytes by major histocompatibility complex class I molecules. Proteasome-dependent epitope processing is greatly improved through the interferon-γ-induced formation of immunoproteasomes and the activator complex PA28. Tripeptidyl aminopeptidase II also has a strong effect on epitope generation. With its endoproteolytic and exoproteolytic activities, TPPII acts 'downstream' of the proteasome and relies on products released by the proteasome. The antigen-processing cascade involving different proteolytic systems raises anew the question of how antigenic peptides are generated. We therefore revisit the interferon-γ-induced immune adaptation of the proteasome and attempt to redefine its function in connection with the emerging importance of TPPII.

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Figure 1: The proteasome and antigen processing: the classical pathway.
Figure 2: Formation of immunoproteasomes.
Figure 3: The proteasome and antigen processing: substrate hopping and the dual-proteasome model.

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    Peter M Kloetzel

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Kloetzel, P. Generation of major histocompatibility complex class I antigens: functional interplay between proteasomes and TPPII. Nat Immunol 5, 661–669 (2004). https://doi.org/10.1038/ni1090

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