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

TitleTLR signals induce phagosomal MHC-I delivery from the endosomal recycling compartment to allow cross-presentation.
Publication TypeJournal Article
Year of Publication2014
AuthorsNair-Gupta, P, Baccarini, A, Tung, N, Seyffer, F, Florey, O, Huang, Y, Banerjee, M, Overholtzer, M, Roche, PA, Tampé, R, Brown, BD, Amsen, D, Whiteheart, SW, J Blander, M
JournalCell
Volume158
Issue3
Pagination506-21
Date Published2014 Jul 31
ISSN1097-4172
KeywordsAnimals, Antigen Presentation, Dendritic Cells, Endosomes, Histocompatibility Antigens Class I, Lymphoid Tissue, Mice, Ovalbumin, Phagocytosis, Phagosomes, Phosphorylation, Protein Transport, Qb-SNARE Proteins, Qc-SNARE Proteins, rab GTP-Binding Proteins, Toll-Like Receptors
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.

DOI10.1016/j.cell.2014.04.054
Alternate JournalCell
PubMed ID25083866
PubMed Central IDPMC4212008
Grant ListHL56652 / HL / NHLBI NIH HHS / United States
R01 CA154649 / CA / NCI NIH HHS / United States
R01 AI104848 / AI / NIAID NIH HHS / United States
AI104848 / AI / NIAID NIH HHS / United States
S10-RR0 9145-01 / RR / NCRR NIH HHS / United States
5R24 CA095823-04 / CA / NCI NIH HHS / United States
DK072201 / DK / NIDDK NIH HHS / United States
R01 HL056652 / HL / NHLBI NIH HHS / United States
R01 HL091893 / HL / NHLBI NIH HHS / United States
AI073899 / AI / NIAID NIH HHS / United States
P01 DK072201 / DK / NIDDK NIH HHS / United States
R01 AI073899 / AI / NIAID NIH HHS / United States
AI095245 / AI / NIAID NIH HHS / United States
HL082193 / HL / NHLBI NIH HHS / United States
R01 AI095245 / AI / NIAID NIH HHS / United States
R24 CA095823 / CA / NCI NIH HHS / United States
CA154649 / CA / NCI NIH HHS / United States
L40 HL082193 / HL / NHLBI NIH HHS / United States
R56 AI073899 / AI / NIAID NIH HHS / United States