CD1d-restricted antigen presentation by Vγ9Vδ2-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 alpha-galactosylceramide (alpha-GalCer) and play a dominant role in antitumor immunity. Clinical trials with alpha-GalCer-pulsed monocyte-derived dendritic cells (moDC) have shown anecdotal antitumor activity in advanced cancer. It was reported that phosphoantigen (pAg)-activated V gamma 9V delta 2-T cells can acquire characteristics of professional antigen-presenting cells (APC). Considering the clinical immunotherapeutic applications, V gamma 9V delta 2-T APC can offer important advantages over moDC, potentially constituting an attractive novel APC platform. Here, we demonstrate that V gamma 9V delta 2-T APC can present antigens to iNKT. However, this does not result from de novo synthesis of CD1d by V gamma 9V delta 2-T, but critically depends on trogocytosis of CD1d-containing membrane fragments from pAg-expressing cells. CD1d-expressing V gamma 9V delta 2-T cells were able to activate iNKT in a CD1d-restricted and alpha-GalCer-dependent fashion. Although alpha-GalCerloaded moDC outperformed V gamma 9V delta 2-T APC on a per cell basis, V gamma 9V delta 2-T APC possess unique features with respect to clinical immunotherapeutic application that make them an interesting platform for consideration in future clinical trials. (C) 2014 AACR.