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MHC presentation via autophagy and how viruses escape from it

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Abstract

T cells detect infected and transformed cells via antigen presentation by major histocompatibility complex (MHC) molecules on the cell surface. For T cell stimulation, these MHC molecules present fragments of proteins that are expressed or taken up by the cell. These fragments are generated by distinct proteolytic mechanisms for presentation on MHC class I molecules to cytotoxic CD8+ and on MHC class II molecules to helper CD4+ T cells. Proteasomes are primarily involved in MHC class I ligand and lysosomes, in MHC class II ligand generation. Autophagy delivers cytoplasmic material to lysosomes and, therefore, contributes to cytoplasmic antigen presentation by MHC class II molecules. In addition, it has been recently realized that this process also supports extracellular antigen processing for MHC class II presentation and cross-presentation on MHC class I molecules. Although the exact mechanisms for the regulation of these antigen processing pathways by autophagy are still unknown, recent studies, summarized in this review, suggest that they contribute to immune responses against infections and to maintain tolerance. Moreover, they are targeted by viruses for immune escape and could maybe be harnessed for immunotherapy.

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Acknowledgements

Our research is supported by the National Cancer Institute (R01CA108609 and R01CA101741), the Foundation for the National Institutes of Health (Grand Challenges in Global Health), and the Swiss National Science Foundation (310030_126995).

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  1. Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Winterthurerstrasse 190, CH-8057, Zürich, Switzerland

    Monique Gannage & Christian Münz

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  1. Monique Gannage
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  2. Christian Münz
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Correspondence to Christian Münz.

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This article is published as part of the Special Issue on Autophagy.

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Gannage, M., Münz, C. MHC presentation via autophagy and how viruses escape from it. Semin Immunopathol 32, 373–381 (2010). https://doi.org/10.1007/s00281-010-0227-7

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