title: Long-Peptide Cross-Presentation by Human Dendritic Cells Occurs in Vacuoles by Peptide Exchange on Nascent MHC Class I Molecules.
abstract: Cross-presentation enables dendritic cells to present on their MHC class I molecules antigenic peptides derived from exogenous material, through a mechanism that remains partly unclear. It is particularly efficient with long peptides, which are used in cancer vaccines. We studied the mechanism of long-peptide cross-presentation using human dendritic cells and specific CTL clones against melanoma Ags gp100 and Melan-A/MART1. We found that cross-presentation of those long peptides does not depend on the proteasome or the transporter associated with Ag processing, and therefore follows a vacuolar pathway. We also observed that it makes use of newly synthesized MHC class I molecules, through peptide exchange in vesicles distinct from the endoplasmic reticulum and classical secretory pathway, in an SEC22b- and CD74-independent manner. Our results indicate a nonclassical secretion pathway followed by nascent HLA-I molecules that are used for cross-presentation of those long melanoma peptides in the vacuolar pathway. Our results may have implications for the development of vaccines based on long peptides.
authors.affiliation: Ludwig Institute for Cancer Research, Brussels B-1200, Belgium; Walloon Excellence in Life Sciences and Biotechnology, Brussels B-1200, Belgium; de Duve Institute, Université Catholique de Louvain, Brussels B-1200, Belgium;
authors.forename: Wenbin
authors.initials: W
authors.lastname: Ma
authors.affiliation: Ludwig Institute for Cancer Research, Brussels B-1200, Belgium; de Duve Institute, Université Catholique de Louvain, Brussels B-1200, Belgium; The Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China; Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China; and.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Ludwig Institute for Cancer Research, Brussels B-1200, Belgium; Walloon Excellence in Life Sciences and Biotechnology, Brussels B-1200, Belgium; de Duve Institute, Université Catholique de Louvain, Brussels B-1200, Belgium;
authors.forename: Nathalie
authors.initials: N
authors.lastname: Vigneron
authors.affiliation: Ludwig Institute for Cancer Research, Brussels B-1200, Belgium; de Duve Institute, Université Catholique de Louvain, Brussels B-1200, Belgium;
authors.forename: Vincent
authors.initials: V
authors.lastname: Stroobant
authors.affiliation: Laboratory of Molecular and Cellular Therapy, Department of Physiology and Immunology, Vrije Universiteit Brussel, Brussels B-1090, Belgium.
authors.forename: Kris
authors.initials: K
authors.lastname: Thielemans
authors.affiliation: Ludwig Institute for Cancer Research, Brussels B-1200, Belgium; Walloon Excellence in Life Sciences and Biotechnology, Brussels B-1200, Belgium; de Duve Institute, Université Catholique de Louvain, Brussels B-1200, Belgium;
authors.forename: Pierre
authors.initials: P
authors.lastname: van der Bruggen
authors.affiliation: Ludwig Institute for Cancer Research, Brussels B-1200, Belgium; Walloon Excellence in Life Sciences and Biotechnology, Brussels B-1200, Belgium; de Duve Institute, Université Catholique de Louvain, Brussels B-1200, Belgium; Benoit.Vandeneynde@bru.licr.org.
authors.forename: Benoît J
authors.initials: BJ
authors.lastname: Van den Eynde
mesh_terms: D017951:Antigen Presentation / Q000276:immunology*; D002460:Cell Line; D002478:Cells, Cultured; D045142:Cross-Priming / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D010455:Peptides / Q000276:immunology; D046988:Proteasome Endopeptidase Complex / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014617:Vacuoles / Q000276:immunology*; D058951:gp100 Melanoma Antigen / Q000276:immunology*
chemical_list: D015395:Histocompatibility Antigens Class I; D010455:Peptides; D058951:gp100 Melanoma Antigen; D046988:Proteasome Endopeptidase Complex