T-cell engagement of dendritic cells rapidly rearranges MHC class II transport

Abstract

Assembly of major histocompatibility complex (MHC) molecules, which present antigen in the form of short peptides to T lymphocytes, occurs in the endoplasmic reticulum; once assembled, these molecules travel from the endoplasmic reticulum to their final destination. MHC class II molecules follow a route that takes them by means of the endocytic pathway, where they acquire peptide, to the cell surface. The transport of MHC class II molecules in 'professional' antigen-presenting cells (APCs) is subject to tight control and responds to inflammatory stimuli such as lipopolysaccharide. To study class II transport in live APCs, we replaced the mouse MHC class II gene with a version that codes for a class II molecule tagged with enhanced green fluorescent protein (EGFP). The resulting mice are immunologically indistinguishable from wild type. In bone-marrow-derived dendritic cells, we observed class II molecules in late endocytic structures with transport patterns similar to those in Langerhans cells observed in situ. We show that tubular endosomes extend intracellularly and polarize towards the interacting T cell, but only when antigen-laden dendritic cells encounter T cells of the appropriate specificity. We propose that such tubulation serves to facilitate the ensuing T-cell response.

Requirement for Phosphoinositide 3-Kinase p110δ Signaling in B Cell Antigen Receptor-Mediated Antigen Presentation

“…6A and data not shown), suggesting that the polarization of B cell Agprocessing compartments may facilitate directional trafficking of loaded peptide-MHC complexes to the B cell surface facing the T cells, enhancing Ag presentation. Such directional trafficking has been reported recently in dendritic cells (54,55), and raises the intriguing possibility that PI3K signaling may be required for targeted release of peptide-MHC II complexes generated via BCRmediated uptake.…”

MHC Class II Antigen Presentation by Dendritic Cells Regulated through Endosomal Sorting

“…In this case, a pathway should exist for pMHCII to travel back from ILVs to the endosomal-delimiting membrane from where it could then reach the plasma membrane. Such a pathway, also referred to as "back-fusion" or retrofusion of ILVs, was also proposed to explain the disappearance of the MVB during DC maturation (Kleijmeer et al 2001) and to provide a source of membrane needed for the formation of MIIC-associated tubules in maturing DCs (Boes et al 2002(Boes et al , 2003Chow et al 2002;Vyas et al 2007). More recently, however, it was shown that such membrane tubules can be generated as a consequence of homotypic endosome fusion (Skjeldal et al 2012), which is accelerated in maturing DCs (van Nispen tot Pannerden et al 2010).…”

“…Maintenance of MHCII ubiquitination in endocytic compartments other than phagosomes within the same cell would enhance selectivity in MHCII presentation of pathogen-derived peptides. Transfer of pMHCII from pathogen-loaded phagosomes to the plasma membrane can occur unidirectionally, for example, toward immunological synapse between DC and T cells (Boes et al 2002;Keller et al 2007), applying yet another layer of specificity.…”

“…In maturing DCs, transport of MHCII is mediated via membrane tubules that radiate out from the MIIC toward the plasma membrane, and this pathway depends on an intact microtubule network (Kleijmeer et al 2001;Boes et al 2002Boes et al , 2003Chow et al 2002;Vyas et al 2007;van Nispen tot Pannerden et al 2010). MHCII, DM, and LAMP1 are not enriched in these tubules relative to the vacuolar endosomes from which they derive, suggesting that this pathway may not require active recruitment but is entered by default (Kleijmeer et al 2001).…”

Synapses immunologiques et synapses neuronales

“…Des mécanismes antérogrades doivent aussi être pris en compte. Ainsi, lors des interactions T-DC, des réponses calciques [18] et des polarisations dynamiques d'actine dans les DC [49] ont été observées, suivies de l'envoi, par les DC, de chapelets de vésicules chargées en CMH de classe II [50]. Les DC reçoi-vent donc, des lymphocytes T, des signaux précoces qui peuvent influencer la formation de la synapse T-DC.…”