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Canonical and Non-Canonical Functions of the Autophagy Machinery in MHC Restricted Antigen Presentation


Münz, Christian (2022). Canonical and Non-Canonical Functions of the Autophagy Machinery in MHC Restricted Antigen Presentation. Frontiers in Immunology, 13:868888.

Abstract

Macroautophagy delivers cytoplasmic constituents for lysosomal degradation. Since major histocompatibility complex (MHC) class II molecules sample peptides after lysosomal degradation for presentation to CD4$^{+}$ T cells, it was originally described that these peptides can also originate from macroautophagy substrates. In recent years it has become clear that in addition to this canonical function of the macroautophagy machinery during MHC class II restricted antigen presentation at least parts of this machinery are also used to regulate phagocytosis of antigens, degradation of MHC class I molecules, and unconventional secretion of antigens in extracellular vesicles, including virus particles. This review discusses how both canonical and non-canonical functions of the macroautophagy machinery influence antigen presentation on MHC class I and II molecules to CD8$^{+}$ and CD4$^{+}$ T cells. A better understanding of the molecular mechanisms by which the macroautophagy machinery is distributed between its canonical and non-canonical functions should allow targeting of antigens to these different pathways to influence MHC restricted presentation during vaccination against infectious diseases and tumors.

Abstract

Macroautophagy delivers cytoplasmic constituents for lysosomal degradation. Since major histocompatibility complex (MHC) class II molecules sample peptides after lysosomal degradation for presentation to CD4$^{+}$ T cells, it was originally described that these peptides can also originate from macroautophagy substrates. In recent years it has become clear that in addition to this canonical function of the macroautophagy machinery during MHC class II restricted antigen presentation at least parts of this machinery are also used to regulate phagocytosis of antigens, degradation of MHC class I molecules, and unconventional secretion of antigens in extracellular vesicles, including virus particles. This review discusses how both canonical and non-canonical functions of the macroautophagy machinery influence antigen presentation on MHC class I and II molecules to CD8$^{+}$ and CD4$^{+}$ T cells. A better understanding of the molecular mechanisms by which the macroautophagy machinery is distributed between its canonical and non-canonical functions should allow targeting of antigens to these different pathways to influence MHC restricted presentation during vaccination against infectious diseases and tumors.

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Additional indexing

Item Type:Journal Article, refereed, further contribution
Communities & Collections:04 Faculty of Medicine > Institute of Experimental Immunology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Scopus Subject Areas:Health Sciences > Immunology and Allergy
Life Sciences > Immunology
Uncontrolled Keywords:Immunology, Immunology and Allergy
Language:English
Date:4 March 2022
Deposited On:30 Jan 2023 10:51
Last Modified:30 Dec 2023 02:42
Publisher:Frontiers Research Foundation
ISSN:1664-3224
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.3389/fimmu.2022.868888
PubMed ID:35309359
Project Information:
  • : FunderSwiss Vaccine Research Institute
  • : Grant ID
  • : Project Title
  • Content: Published Version
  • Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)