Review
doi: 10.1016/j.coi.2016.03.004. Epub 2016 Mar 25.The melting pot of the MHC II peptidome
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- PMCID: PMC4884503
- DOI: 10.1016/j.coi.2016.03.004
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Review
The melting pot of the MHC II peptidome
Lawrence J Stern et al. Curr Opin Immunol.2016 Jun.
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Abstract
Recent advances in mass spectrometry technology have facilitated detailed examination of MHC-II immunopeptidomes, for example the repertoires of peptides bound to MHC-II molecules expressed in antigen presenting cells. These studies have deepened our view of MHC-II presentation. Other studies have broadened our view of pathways leading up to peptide loading. Here we review these recent studies in the context of earlier work on conventional and non-conventional MHC-II processing. The message that emerges is that sources of antigen beyond conventional endosomal processing of endocytosed proteins are important for generation of cellular immune responses to pathogens and maintenance of central and peripheral tolerance. The multiplicity of pathways results in a broad MHC II immunopeptidome that conveys the sampled environment to patrolling T cells.
Copyright © 2016 Elsevier Ltd. All rights reserved.
Figures
Intracellular sites for conventional and non-conventional loading onto MHC II proteins. Extracellular antigens or cell-surface proteins can enter the MHC II pathway through a conventional route of endocytosis followed by proteolysis and MHC II loading in late endosomes or lysosomes. Alternate pathways for antigen entry include macroautophagy (MA), endosomal microautophagy (eMI), or chaperone-mediated autophagy (CMI), which bring proteins into late endosomes or lysosomes for processing and loading. Antigens can be loaded onto MHC II proteins also at the cell surface or in recycling, sorting, or early endosomes. Because of lower proteolytic activity in these compartments this pathway is likely to be more important for preprocessed peptides, for example from lymph, or for unfolded proteins. DM activity increases with endosomal maturation, in part because of DO dissociation from DM at low pH [107], and so DM-sensitive antigens are more likely to be loaded in early compartments, and loading in late compartments more likely to be restricted to DM-resistant antigens.
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