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

P Nair-Gupta, A Baccarini, N Tung, F Seyffer, O Florey… - Cell, 2014 - cell.com
P Nair-Gupta, A Baccarini, N Tung, F Seyffer, O Florey, Y Huang, M Banerjee, M Overholtzer…
Cell, 2014cell.com
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 …
Summary
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.
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