MHC class II compartment subtypes: structure and function
Introduction
Late endosomes and lysosomal organelles are sub-cellular compartments, which in all cell types are the site of degradation of both endogenous and exogenous materials [1]. These organelles are characterized by acidic pH, the presence of proteases and expression of lysosome-associated membrane protein (Lamp) protein family members [2, 3]. Lysosomal compartments are used also in several immune and non-immune cell types to perform specific functions distinct from protein degradation. Indeed, in professional antigen presenting cells, late endosomes and lysosomes are enriched in MHC class II proteins and in other molecules involved in peptide processing, loading and editing (human leukocyte antigen [HLA]-DM, HLA-DO, gamma-interferon-inducible lysosomal thiol reductase, and cathepsins), and become specialized organelles termed MIICs (for MHC class II containing compartments). It is in these that most antigen processing and MHC class II loading occurs [4, 5]. The observations that MIIC can appear with different morphologies — multivesicular, multilamellar, or a combination of both — and that these differences are likely to reflect different maturative stages, have long been appreciated [6, 7]. However, the biological significance associated with the different morphologies and the exact contribution of each compartment to antigen processing and MHC class II loading processes are still ill-defined (Figure 1). During the past couple of years, several reports have begun to shed light on the relationship between MIIC biogenesis, ultrastructural morphology, protein composition and specific roles in antigen processing and presentation.
This new body of information will be the focus of this review. Contribution of the molecular mechanism of endosomal protein sorting (endosomal sorting complexes required for transport [ESCORT], ubiquination and adaptor protein complexes [AP]-1, -2, -3 and -4 adaptors), which also play a role in endosomal formation and trafficking, have been extensively discussed in other reviews and will not be discussed here [8, 9].
Section snippets
Multivesicular MIIC
Multivesicular bodies (MVBs) are a type of MIICs that have a diameter of between 400 and 500 nm. They are composed of a limiting membrane that encloses several internal vesicles that have diameters of between 40 and 90 nm [10, 11]. They are commonly described as late endosomal compartments and are enriched in MHC class II proteins. MVBs receive bio-synthetic cargo from the trans-Golgi network, as well as molecules that have been internalized by way of endocytosis [5]. An increasing interest is
Multilamellar MIIC
A lysosomal-like compartment formed by concentric lamellae and particularly enriched in MHC class II molecules was the first MIIC to be identified [32] (Figure 1). These multilamellar bodies (MLBs) are more specifically expressed in APCs, such as DCs, B cells and macrophages [33, 34, 35], compared with MVBs, which are ubiquitously distributed. The biogenesis of MLBs appears to be dependent on the presence of MHC class II and Ii. In fact, transfection of kidney epithelial cells that had both of
Electrondense bodies
Electron dense bodies (EDBs) have recently been described as a novel lysosomal-like MIIC (Lamp-1+, HLA-DR+ and HLA-DM+) that is present in peripheral CD14+ human monocytes [18••] (Figure 1). These compartments are delimitated by a single perimetral membrane and are occupied by electrondense material. Among APCs and related cell types, these compartments have, to date, been found together with MVBs in human monocytes and in pre-DC populations [18••]. EDBs have a similar structure to the
Conclusions
The differential ultrastructure of MVBs and MLBs, reflective of their differential lipid and protein composition, has long been known. However, the degree to which this differential endosomal morphology affects antigen presentation has only begun to be appreciated. It has recently been reported that differential loading pathways produce distinct MHC class II–peptide conformers that differentially prime T cells [44, 45••]. MHC class II–peptide complexes formed in late endosomal and lysosomal
References and recommended reading
Papers of particular interest, published within the annual period of review, have been highlighted as:
• of special interest
•• of outstanding interest
Acknowledgements
We would like to thank Sebastian Amigorena for critical reading of the review
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Multivesicular bodies containing exosomes in immune-related cells of the intestine in zebrafish (Danio rerio): Ultrastructural evidence
2019, Fish and Shellfish ImmunologyCitation Excerpt :To investigate whether MVBs and their exosomes are associated with the mucin maturation process, we observed that MVBs with a small number of exosomes were located among many mature mucin granules in the apical cytoplasm of goblet cells. Two types of MVBs have been identified in professional antigen presenting cells (APCs), such as dendritic cells [24], oligodendroglia cells [25] and absorptive cells [14]. We identified that two-types of MVBs exist in the cytoplasm around mature mucin granules.
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2019, Fish and Shellfish ImmunologyCitation Excerpt :In terms of the differences in size, electron density, and number of ILVs, we defined mature le as “heterogenous” MVBs in the zebrafish gut. There are two types of MVBs in mammalian professional antigen presenting cells (APCs), e.g., lymphocyte or dendritic cells, and these MVBs are defined by their expression of major histocompatibility complex (MHC)-Ⅱ-enriched compartments (MⅡCs) and exert immune function [35,36]. It was first reported that abundant “heterogenous” MVBs were enriched in the apical cytoplasm of the absorptive cells in this study.
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2013, Handbook of Biologically Active PeptidesAge-related oxidative stress compromises endosomal proteostasis
2012, Cell ReportsCitation Excerpt :In addition extracellular aggregates organized as amyloid-like structures can also reach late endosomes and lysosomes of tissue-resident macrophages and dendritic cells (DCs) after being phagocytosed (Chiti and Dobson, 2006; Alavez et al., 2011; Devitt and Marshall, 2011). In endosomes/lysosomes most of the damaged biomolecules are degraded to their constitutive basic components by acidic hydrolases (Stern et al., 2006). However, the nature of the oxidized amino acid has an impact on protein turnover in that o- and m-tyrosines increase protein catabolism, whereas proteins with DOPA modifications are inefficiently degraded and tend to generate high-molecular weight (MW) SDS-stable aggregates (Dyer et al., 1993; Oliver et al., 1987; Requena et al., 2001; Dalle-Donne et al., 2003; Isom et al., 2004; Dunlop et al., 2008, 2009; Madian and Regnier, 2010).