Titre
3-D Structure of multilaminar lysosomes in antigen presenting cells reveals trapping of MHC II on the internal membranes.
Type
article
Institution
Externe
Périodique
Auteur(s)
Murk, J.L.
Auteure/Auteur
Lebbink, M.N.
Auteure/Auteur
Humbel, B.M.
Auteure/Auteur
Geerts, W.J.
Auteure/Auteur
Griffith, J.M.
Auteure/Auteur
Langenberg, D.M.
Auteure/Auteur
Verreck, F.A.
Auteure/Auteur
Verkleij, A.J.
Auteure/Auteur
Koster, A.J.
Auteure/Auteur
Geuze, H.J.
Auteure/Auteur
Kleijmeer, M.J.
Auteure/Auteur
Liens vers les personnes
ISSN
1398-9219
Statut éditorial
Publié
Date de publication
2004
Volume
5
Numéro
12
Première page
936
Dernière page/numéro d’article
945
Langue
anglais
Résumé
In late endosomes and lysosomes of antigen presenting cells major histocompatibility complex class II (MHC II) molecules bind peptides from degraded internalized pathogens. These compartments are called MHC class II compartments (MIICs), and from here peptide-loaded MHC II is transported to the cell surface for presentation to helper T-lymphocytes to generate an immune response. Recent studies from our group in mouse dendritic cells indicate that the MHC class II on internal vesicles of multivesicular late endosomes or multivesicular bodies is the main source of MHC II at the plasma membrane. We showed that dendritic cell activation triggers a back fusion mechanism whereby MHC II from the inner membranes is delivered to the multivesicular bodies' outer membrane. Another type of MIIC in B-lymphocytes and dendritic cells is more related to lysosomes and often appears as a multilaminar organelle with abundant MHC II-enriched internal membrane sheets. These multilaminar lysosomes have a functioning peptide-loading machinery, but to date it is not clear whether peptide-loaded MHC II molecules from the internal membranes can make their way to the cell surface and contribute to T cell activation. To obtain detailed information on the membrane organization of multilaminar lysosomes and investigate possible escape routes from the lumen of this organelle, we performed electron tomography on cryo-immobilized B-lymphocytes and dendritic cells. Our high-resolution 3-D reconstructions of multilaminar lysosomes indicate that their membranes are organized in such a way that MHC class II may be trapped on the inner membranes, without the possibility to escape to the cell surface.
PID Serval
serval:BIB_54E63CB2941D
PMID
Open Access
Oui
Date de création
2012-10-18T13:18:53.629Z
Date de création dans IRIS
2025-05-20T17:58:51Z