TAP dysfunction in dendritic cells enables noncanonical cross-presentation for T cell priming.

ABSTRACT: 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 interme

SUBMITTER: Barbet G 

PROVIDER: S-EPMC8981674 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature