Dynamics within tetraspanin pairs affect MHC class II expression

Hoorn, Tineke van den; Paul, Petra; Janssen, Lennert; Janssen, Hans; Neefjes, Jacques

doi:10.1242/jcs.088047

Cited by 30 publications

(26 citation statements)

References 37 publications

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“…Although the absence of CD9 in MoDCs did not alter the expression of adhesion molecules or the IS formation, it significantly impaired CD4 ϩ T cell activation, suggesting that CD9 regulates Ag presentation. This effect does not seem to be related to an impairment of MHC-II coupling to antigenic peptides, since it was previously shown that CD9 knockdown in DC does not affect MHC-II peptide loading (44). In this regard, we did not observe differences in Ag proteolytic processing in CD9 KO MoDCs.…”

Section: Discussionsupporting

confidence: 54%

“…These molecules associate with tetraspanins CD63 and CD82 on both MIIC subdomains (41,42,44), with CD63 stably interacting with MHC-II and CD82 with HLA-DM (44). CD63 regulates peptide-loaded MHC-II surface expression and could act as a cochaperone (44). We have investigated the colocalization of MHC-II with different markers of intracellular vesicles.…”

Section: Discussionmentioning

confidence: 99%

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CD9 Regulates Major Histocompatibility Complex Class II Trafficking in Monocyte-Derived Dendritic Cells

Rocha-Perugini

Hoyo

González-Granado

et al. 2017

Molecular and Cellular Biology

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Antigen presentation by dendritic cells (DCs) stimulates naive CD4 ϩ T cells, triggering T cell activation and the adaptive arm of the immune response. Newly synthesized major histocompatibility complex class II (MHC-II) molecules accumulate at MHC-II-enriched endosomal compartments and are transported to the plasma membrane of DCs after binding to antigenic peptides to enable antigen presentation. In DCs, MHC-II molecules are included in tetraspanin-enriched microdomains (TEMs). However, the role of tetraspanin CD9 in these processes remains largely undefined. Here, we show that CD9 regulates the T cell-stimulatory capacity of granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent bone marrow-derived DCs (BMDCs), without affecting antigen presentation by fms-like tyrosine kinase 3 ligand (Flt3L)-dependent BMDCs. CD9 knockout (KO) GM-CSF-dependent BMDCs, which resemble monocyte-derived DCs (MoDCs), induce lower levels of T cell activation than wild-type DCs, and this effect is related to a reduction in MHC-II surface expression in CD9-deficient MoDCs. Importantly, MHC-II targeting to the plasma membrane is largely impaired in immature CD9 KO MoDCs, in which MHC-II remains arrested in acidic intracellular compartments enriched in LAMP-1 (lysosome-associated membrane protein 1), and MHC-II internalization is also blocked. Moreover, CD9 participates in MHC-II trafficking in mature MoDCs, regulating its endocytosis and recycling. Our results demonstrate that the tetraspanin CD9 specifically regulates antigenic presentation in MoDCs through the regulation of MHC-II intracellular trafficking.

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Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 99%

CD9 Regulates Major Histocompatibility Complex Class II Trafficking in Monocyte-Derived Dendritic Cells

Rocha-Perugini

Hoyo

González-Granado

et al. 2017

Molecular and Cellular Biology

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“…Within endosomal compartments, CD9, CD63, and CD81 all were important for controlling surface expression of MHC II (37). Tetraspanins can also associate with class II molecules on the surface (38).…”

Section: Lipid Domains and Other Microdomainsmentioning

confidence: 99%

Organizing MHC Class II Presentation

Fooksman

2014

Front. Immunol.

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Major histocompatibility complex (MHC) class II molecules are ligands for CD4+ T cells and are critical for initiating the adaptive immune response. This review is focused on what is currently known about MHC class II organization at the plasma membrane of antigen presenting cells and how this affects antigen presentation to T cells. The organization and diffusion of class II molecules have been measured by a variety of biochemical and microscopic techniques. Membrane lipids and other proteins have been implicated in MHC class II organization and function. However, when compared with the organization of MHC class I or TCR complexes, much less is known about MHC class II. Since clustering of T cell receptors occurs during activation, the organization of MHC molecules prior to recognition and during synapse formation may be critical for antigen presentation.

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“…An enlargement of gB/CD63/DR-costained vesicles was observed in some cell types, usually upon the overexpression of gB [19,23]. In addition, CD63 stably interacts with MHC II at MVB, including ILV, and controls MHC II expression [46]. Therefore, the CD63-MHC II association may be important for exosomal MHC secretion.…”

Section: Alphaherpesvirus Gb Homologs Affect Mhc Class Ii-cd63 Traffimentioning

confidence: 99%

Alphaherpesvirus gB Homologs Are Targeted to Extracellular Vesicles, but They Differentially Affect MHC Class II Molecules

Grabowska

Wąchalska

Graul

et al. 2020

Viruses

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Herpesvirus envelope glycoprotein B (gB) is one of the best-documented extracellular vesicle (EVs)-incorporated viral proteins. Regarding the sequence and structure conservation between gB homologs, we asked whether bovine herpesvirus-1 (BoHV-1) and pseudorabies virus (PRV)-encoded gB share the property of herpes simplex-1 (HSV-1) gB to be trafficked to EVs and affect major histocompatibility complex (MHC) class II. Our data highlight some conserved and differential features of the three gBs. We demonstrate that mature, fully processed BoHV-1 and PRV gBs localize to EVs isolated from constructed stable cell lines and EVs-enriched fractions from virus-infected cells. gB also shares the ability to co-localize with CD63 and MHC II in late endosomes. However, we report here a differential effect of the HSV-1, BoHV-1, and PRV glycoprotein on the surface MHC II levels, and MHC II loading to EVs in stable cell lines, which may result from their adverse ability to bind HLA-DR, with PRV gB being the most divergent. BoHV-1 and HSV-1 gB could retard HLA-DR exports to the plasma membrane. Our results confirm that the differential effect of gB on MHC II may require various mechanisms, either dependent on its complex formation or on inducing general alterations to the vesicular transport. EVs from virus-infected cells also contained other viral glycoproteins, like gD or gE, and they were enriched in MHC II. As shown for BoHV-1 gB-or BoHV-1-infected cell-derived vesicles, those EVs could bind anti-virus antibodies in ELISA, which supports the immunoregulatory potential of alphaherpesvirus gB.

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Dynamics within tetraspanin pairs affect MHC class II expression

Cited by 30 publications

References 37 publications

CD9 Regulates Major Histocompatibility Complex Class II Trafficking in Monocyte-Derived Dendritic Cells

CD9 Regulates Major Histocompatibility Complex Class II Trafficking in Monocyte-Derived Dendritic Cells

Organizing MHC Class II Presentation

Alphaherpesvirus gB Homologs Are Targeted to Extracellular Vesicles, but They Differentially Affect MHC Class II Molecules

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