TLR signals induce phagosomal MHC-I delivery from the endosomal recycling compartment to allow cross-presentation Journal Article

   

Authors:	Nair-Gupta, P.; Baccarini, A.; Tung, N.; Seyffer, F.; Florey, O.; Huang, Y.; Banerjee, M.; Overholtzer, M.; Roche, P. A.; Tampé, R.; Brown, B. D.; Amsen, D.; Whiteheart, S. W.; Blander, J. M.
Article Title:	TLR signals induce phagosomal MHC-I delivery from the endosomal recycling compartment to allow cross-presentation
Abstract:	Adaptation of the endoplasmic reticulum (ER) pathway for MHC class I (MHC-I) presentation in dendritic cells enables cross-presentation of peptides derived from phagocytosed microbes, infected cells, or tumor cells to CD8 T cells. How these peptides intersect with MHC-I molecules remains poorly understood. Here, we show that MHC-I selectively accumulate within phagosomes carrying microbial components, which engage Toll-like receptor (TLR) signaling. Although cross-presentation requires Sec22b-mediated phagosomal recruitment of the peptide loading complex from the ER-Golgi intermediate compartment (ERGIC), this step is independent of TLR signaling and does not deliver MHC-I. Instead, MHC-I are recruited from an endosomal recycling compartment (ERC), which is marked by Rab11a, VAMP3/cellubrevin, and VAMP8/endobrevin and holds large reserves of MHC-I. While Rab11a activity stocks ERC stores with MHC-I, MyD88-dependent TLR signals drive IκB-kinase (IKK)2-mediated phosphorylation of phagosome-associated SNAP23. Phospho-SNAP23 stabilizes SNARE complexes orchestrating ERC-phagosome fusion, enrichment of phagosomes with ERC-derived MHC-I, and subsequent cross-presentation during infection. PaperFlick © 2014 Elsevier Inc.
Keywords:	signal transduction; controlled study; unclassified drug; nonhuman; cd8 antigen; cd8+ t lymphocyte; animal cell; mouse; cell compartmentalization; complex formation; infection; dendritic cell; cell protein; endoplasmic reticulum; phagocytosis; phagosome; myeloid differentiation factor 88; toll like receptor; i kappa b kinase; major histocompatibility antigen class 1; endosome; golgi complex; cross presentation; snare protein; priority journal; article; cellubrevin; protein rab11a; protein sec22b; protein snap23; protein vamp8; endosomal recycling compartment
Journal Title:	Cell
Volume:	158
Issue:	3
ISSN:	0092-8674
Publisher:	Cell Press
Date Published:	2014-07-31
Start Page:	506
End Page:	521
Language:	English
DOI:	10.1016/j.cell.2014.04.054
PROVIDER:	scopus
PUBMED:	25083866
PMCID:	PMC4212008
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84905402595&partnerID=40&md5=ebf2ee278537cba1e93f4c67b7916a0d
Notes:	Export Date: 2 September 2014 -- CODEN: CELLB -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/58098