Long-Peptide Cross-Presentation by Human Dendritic Cells Occurs in Vacuoles by Peptide Exchange on Nascent MHC Class I Molecules

Wenbin Ma, Yi Zhang, Nathalie Vigneron, Vincent Stroobant, Kris Thielemans, Pierre van der Bruggen, Benoît J Van den Eynde

Research output: Contribution to journalArticle

28 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1711-1720
Number of pages10
JournalJournal of Immunology
Volume196
Issue number4
DOIs
Publication statusPublished - 15 Feb 2016

Keywords

  • Antigen Presentation
  • Cell Line
  • Cells, Cultured
  • Cross-Priming
  • Dendritic Cells
  • Histocompatibility Antigens Class I
  • Humans
  • Peptides
  • Proteasome Endopeptidase Complex
  • T-Lymphocytes, Cytotoxic
  • Vacuoles
  • gp100 Melanoma Antigen
  • Research Support, Non-U.S. Gov't

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