CD1d-Restricted Antigen Presentation by Vg9Vd2-T Cells Requires Trogocytosis

CD1d-restricted invariant natural killer T cells (iNKT) constitute an important immunoregulatory T-cell subset that can be activated by the synthetic glycolipid a-galactosylceramide (a-GalCer) and play a dominant role in antitumor immunity. Clinical trials with a-GalCer–pulsed monocyte-derived dendritic cells (moDC) have shown anecdotal antitumor activity in advanced cancer. It was reported that phosphoantigen (pAg)-activated Vg9Vd2-T cells can acquire characteristics of professional antigen-presenting cells (APC). Considering the clinical immunotherapeutic applications, Vg9Vd2-T APC can offer important advantages over moDC, potentially constituting an attractive novel APC platform. Here, we demonstrate that Vg9Vd2-T APC can present antigens to iNKT. However, this does not result from de novo synthesis of CD1d by Vg9Vd2-T, but critically depends on trogocytosis of CD1d-containing membrane fragments from pAg-expressing cells. CD1d-expressing Vg9Vd2-T cells were able to activate iNKT in a CD1d-restricted and a-GalCer–dependent fashion. Although a-GalCer– loaded moDC outperformed Vg9Vd2-T APC on a per cell basis, Vg9Vd2-T APC possess unique features with respect to clinical immunotherapeutic application that make them an interesting platform for consideration in future clinical trials. Cancer Immunol Res; 2(8); 732–40. 2014 AACR.