| First Author | Barbet G | Year | 2021 |
| Journal | Nat Immunol | Volume | 22 |
| Issue | 4 | Pages | 497-509 |
| PubMed ID | 33790474 | Mgi Jnum | J:306896 |
| Mgi Id | MGI:6706716 | Doi | 10.1038/s41590-021-00903-7 |
| Citation | Barbet G, et al. (2021) TAP dysfunction in dendritic cells enables noncanonical cross-presentation for T cell priming. Nat Immunol 22(4):497-509 |
| abstractText | Classic major histocompatibility complex class I (MHC-I) presentation relies on shuttling cytosolic peptides into the endoplasmic reticulum (ER) by the transporter associated with antigen processing (TAP). Viruses disable TAP to block MHC-I presentation and evade cytotoxic CD8(+) T cells. Priming CD8(+) T cells against these viruses is thought to rely solely on cross-presentation by uninfected TAP-functional dendritic cells. We found that protective CD8(+) T cells could be mobilized during viral infection even when TAP was absent in all hematopoietic cells. TAP blockade depleted the endosomal recycling compartment of MHC-I molecules and, as such, impaired Toll-like receptor-regulated cross-presentation. Instead, MHC-I molecules accumulated in the ER-Golgi intermediate compartment (ERGIC), sequestered away from Toll-like receptor control, and coopted ER-SNARE Sec22b-mediated vesicular traffic to intersect with internalized antigen and rescue cross-presentation. Thus, when classic MHC-I presentation and endosomal recycling compartment-dependent cross-presentation are impaired in dendritic cells, cell-autonomous noncanonical cross-presentation relying on ERGIC-derived MHC-I counters TAP dysfunction to nevertheless mediate CD8(+) T cell priming. |
