Recognition targets of Vδ2- γδ T cells; Shared activating ligands in cancer and CMV infection?

Abstract

Recently, Vδ2- γδ T cells have been shown to be reactive against both cytomegalovirus (CMV)-infected cells and tumor cells. This dual reactivity can be important for clinical application after allogeneic stem cell transplantation, since CMV-infection causes morbidity and mortality in these patients. The dual reactive Vδ2- γδ T cells could be interesting as a treatment for these patients, since these cells are known to kill tumor cells, while at the same time control CMV infection and reactivation. The dual reactivity of Vδ2- γδ T is most likely caused by antigens expressed on both tumor and CMV-infected cells. Until now, only a few antigens are identified for γδ T cells which are mainly recognized by Vδ2+ γδ T cells. This review presents possible antigens for Vδ2- γδ T cells which might underlie the dual reactivity of these T cells. This review is focused on the MHC superfamily, since known ligands of γδ T cells are members of this family, and on tumor antigens, which are known to be overexpressed by tumors. Most of the found possible candidates were tumor antigens, like heat shock proteins (HSP60 and HSP70), adhesion molecules (ICAM-1, CD44, and 1 integrins), and IFITM1. Besides tumor antigens, also some members of the MHC superfamily are considered to be possible antigens underlying the dual reactivity, namely MICA*008 and EPCR