title: CD1d-restricted antigen presentation by Vγ9Vδ2-T cells requires trogocytosis.
abstract: CD1d-restricted invariant natural killer T cells (iNKT) constitute an important immunoregulatory T-cell subset that can be activated by the synthetic glycolipid α-galactosylceramide (α-GalCer) and play a dominant role in antitumor immunity. Clinical trials with α-GalCer-pulsed monocyte-derived dendritic cells (moDC) have shown anecdotal antitumor activity in advanced cancer. It was reported that phosphoantigen (pAg)-activated Vγ9Vδ2-T cells can acquire characteristics of professional antigen-presenting cells (APC). Considering the clinical immunotherapeutic applications, Vγ9Vδ2-T APC can offer important advantages over moDC, potentially constituting an attractive novel APC platform. Here, we demonstrate that Vγ9Vδ2-T APC can present antigens to iNKT. However, this does not result from de novo synthesis of CD1d by Vγ9Vδ2-T, but critically depends on trogocytosis of CD1d-containing membrane fragments from pAg-expressing cells. CD1d-expressing Vγ9Vδ2-T cells were able to activate iNKT in a CD1d-restricted and α-GalCer-dependent fashion. Although α-GalCer-loaded moDC outperformed Vγ9Vδ2-T APC on a per cell basis, Vγ9Vδ2-T APC possess unique features with respect to clinical immunotherapeutic application that make them an interesting platform for consideration in future clinical trials.
authors.affiliation: Departments of Medical Oncology, jj.vandervliet@vumc.nl f.schneiders@vumc.nl.
authors.forename: Famke L
authors.initials: FL
authors.lastname: Schneiders
authors.affiliation: Departments of Medical Oncology.
authors.forename: Jan
authors.initials: J
authors.lastname: Prodöhl
authors.affiliation: Hematology.
authors.forename: Jurjen M
authors.initials: JM
authors.lastname: Ruben
authors.affiliation: Molecular Cell Biology and Immunology, and.
authors.forename: Tom
authors.initials: T
authors.lastname: O'Toole
authors.affiliation: Pathology, VU University Medical Center, Amsterdam, the Netherlands; and.
authors.forename: Rik J
authors.initials: RJ
authors.lastname: Scheper
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U892, Centre de Recherche en Cancérologie Nantes-Angers, Nantes, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Bonneville
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U892, Centre de Recherche en Cancérologie Nantes-Angers, Nantes, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Scotet
authors.affiliation: Departments of Medical Oncology.
authors.forename: Henk M W
authors.initials: HM
authors.lastname: Verheul
authors.affiliation: Departments of Medical Oncology.
authors.forename: Tanja D
authors.initials: TD
authors.lastname: de Gruijl
authors.affiliation: Departments of Medical Oncology, jj.vandervliet@vumc.nl f.schneiders@vumc.nl.
authors.forename: Hans J
authors.initials: HJ
authors.lastname: van der Vliet
mesh_terms: D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology*; D055610:Antigens, CD1d / Q000276:immunology*; D002460:Cell Line; D005699:Galactosylceramides / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology; D055611:Natural Killer T-Cells / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D055610:Antigens, CD1d; D005699:Galactosylceramides; C493154:alpha-galactosylceramide