Abstract

T cells recognize antigen fragments from proteolytic products that are presented to them in the form of peptides on major histocompatibility complex (MHC) molecules, which is crucial for the T cell to identify infected or transformed cells. Autophagy, a process that delivers cytoplasmic constituents for lysosomal degradation, has been observed to provide a substantial source of intra- and extracellular antigens for MHC presentation to T cells, which will impact the tumor-specific immune response. Meanwhile, extracellular components are transported to cytoplasm for the degradation/secretion process by the endo-/exosomal pathway and are thus involved in multiple physiological and pathological processes, including immune responses. Autophagy and endo-/exosomal pathways are intertwined in a highly intricate manner and both are closely involved in antigen processing for MHC presentation; thus, we propose that they may coordinate in antigen processing and presentation in anticancer T cell immune responses. In this article, we discuss the molecular and functional crosstalk between autophagy and endo-/exosomal pathways and their contributions to antigen processing for MHC presentation in anticancer T cell immune responses.

Highlights

  • In eukaryotic cells, major histocompatibility complex (MHC) presentation monitors two proteolytic routes: the ubiquitin-proteasome and the lysosomal systems

  • Recent studies suggest that autophagy and endo-/exosomal pathways are closely involved in antigen processing for MHC presentation, which results in the activation of tumor-specific T cells

  • We focus on the crosstalk between autophagy and endo-/exosomal pathways and their contributions to antigen processing for MHC presentation in cancer

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Summary

Introduction

MHC presentation monitors two proteolytic routes: the ubiquitin-proteasome and the lysosomal systems. Recent studies suggest that autophagy and endo-/exosomal pathways are closely involved in antigen processing for MHC presentation, which results in the activation of tumor-specific T cells. We focus on the crosstalk between autophagy and endo-/exosomal pathways and their contributions to antigen processing for MHC presentation in cancer.

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