title: Intracellular Transport Routes for MHC I and Their Relevance for Antigen Cross-Presentation.
abstract: Cross-presentation, in which exogenous antigens are presented via MHC I complexes, is involved both in the generation of anti-infectious and anti-tumoral cytotoxic CD8(+) T cells and in the maintenance of immune tolerance. While cross-presentation was described almost four decades ago and while it is now established that some dendritic cell (DC) subsets are better than others in processing and cross-presenting internalized antigens, the involved molecular mechanisms remain only partially understood. Some of the least explored molecular mechanisms in cross-presentation concern the origin of cross-presenting MHC I molecules and the cellular compartments where antigenic peptide loading occurs. This review focuses on MHC I molecules and their intracellular trafficking. We discuss the source of cross-presenting MHC I in DCs as well as the role of the endocytic pathway in their recycling from the cell surface. Next, we describe the importance of the TAP peptide transporter for delivering peptides to MHC I during cross-presentation. Finally, we highlight the impact of innate immunity mechanisms on specific antigen cross-presentation mechanisms in which TLR activation modulates MHC I trafficking and TAP localization.
authors.affiliation: INSERM U1149, Faculté Bichat Medical School, ELR8252 CNRS, Center for Research on Inflammation , Paris , France ; Université Paris Diderot, Sorbonne Paris Cité , Paris , France.
authors.forename: Aimé Cézaire
authors.initials: AC
authors.lastname: Adiko
authors.affiliation: INSERM UMR 1163, Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutic Implications , Paris , France ; Université Paris Descartes, Sorbonne Paris Cité , Paris , France ; Imagine Institute , Paris , France.
authors.forename: Joel
authors.initials: J
authors.lastname: Babdor
authors.affiliation: Laboratory of Phagocyte Immunobiology, Peter Gorer Department of Immunobiology, King's College London , London , UK.
authors.forename: Enric
authors.initials: E
authors.lastname: Gutiérrez-Martínez
authors.affiliation: Laboratory of Phagocyte Immunobiology, Peter Gorer Department of Immunobiology, King's College London , London , UK.
authors.forename: Pierre
authors.initials: P
authors.lastname: Guermonprez
authors.affiliation: INSERM U1149, Faculté Bichat Medical School, ELR8252 CNRS, Center for Research on Inflammation , Paris , France ; Université Paris Diderot, Sorbonne Paris Cité , Paris , France.
authors.forename: Loredana
authors.initials: L
authors.lastname: Saveanu
keywords: MHC class I molecules; cross-presentation; dendritic cells; endosomal recycling compartment; tubular endosomes