Details

Autor(en) / Beteiligte

• Nair-Gupta, Priyanka
• Baccarini, Alessia
• Tung, Navpreet
• Seyffer, Fabian
• Florey, Oliver
• Huang, Yunjie
• Banerjee, Meenakshi
• Overholtzer, Michael
• Roche, Paul A.
• Tampé, Robert
• Brown, Brian D.
• Amsen, Derk
• Whiteheart, Sidney W.
• Blander, J. Magarian

Titel

TLR Signals Induce Phagosomal MHC-I Delivery from the Endosomal Recycling Compartment to Allow Cross-Presentation

Ist Teil von

• Cell, 2014-07, Vol.158 (3), p.506-521

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2014

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] [Display omitted] •Rab11a+ cellubrevin+ endobrevin+ ERC hold significant reserves of MHC-I in DC•Rab11a stocks the ERC with “deployment-ready” MHC-I molecules•TLR-MyD88-IKK2 potentiate cross-presentation of peptides derived from phagocytic cargo•MyD88-IKK2 control phagosomal SNAP23 phosphorylation and MHC-I recruitment from ERC In dendritic cells, MHC-I stored in the Rab11a-marked endosomal recycling compartment is delivered to phagosomes for cross-presentation through TLR signaling-dependent and independent mechanisms.