MHC presentation via autophagy and how viruses escape from it |
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Authors: | Monique Gannage Christian Münz |
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Institution: | 1. Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Winterthurerstrasse 190, CH-8057, Zürich, Switzerland
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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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