Open AccessTAP dysfunction in dendritic cells enables noncanonical cross-presentation for T cell priming
Author(s) -
Gaëtan Barbet,
Priyanka Nair-Gupta,
Michael Schotsaert,
Stephen T. Yeung,
Julien Moretti,
Fabian Seyffer,
Giorgi Metreveli,
Thomas J. Gardner,
Angela Choi,
Domenico Tortorella,
Robert Tampé,
Kamal M. Khanna,
Adolfo Garcı́a-Sastre,
J. Magarian Blander
Publication year - 2021
Publication title -
nature immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 9.074
H-Index - 388
eISSN - 1529-2916
pISSN - 1529-2908
DOI - 10.1038/s41590-021-00903-7
Subject(s) - cross presentation , antigen processing , mhc class i , antigen presentation , microbiology and biotechnology , transporter associated with antigen processing , mhc restriction , biology , cytotoxic t cell , major histocompatibility complex , endosome , priming (agriculture) , cd8 , antigen presenting cell , dendritic cell , t cell , antigen , immunology , immune system , intracellular , biochemistry , botany , germination , in vitro
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.