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J Immunol. 2016 Feb 15;196(4):1711-20. doi: 10.4049/jimmunol.1501574. Epub 2016 Jan 20.

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

Author information

1
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;
2
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.
3
Ludwig Institute for Cancer Research, Brussels B-1200, Belgium; de Duve Institute, Université Catholique de Louvain, Brussels B-1200, Belgium;
4
Laboratory of Molecular and Cellular Therapy, Department of Physiology and Immunology, Vrije Universiteit Brussel, Brussels B-1090, Belgium.
5
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.

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.

PMID:
26792804
DOI:
10.4049/jimmunol.1501574
[Indexed for MEDLINE]
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