Cytomegalovirus and tumor stress surveillance by binding of a human γδ T cell antigen receptor to endothelial protein C receptor
Authors list
Carrie R Willcox Vincent Pitard Sonia Netzer Lionel Couzi Mahboob Salim Tobias Silberzahn Jean-François Moreau Adrian Hayday Benjamin E Willcox Julie Déchanet-MervilleAbstract
T cells bearing γδ T cell antigen receptors (TCRs) function in lymphoid stress surveillance. However, the contribution of γδ TCRs to such responses is unclear. Here we found that the TCR of a human V(γ)4V(δ)5 clone directly bound endothelial protein C receptor (EPCR), which allowed γδ T cells to recognize both endothelial cells targeted by cytomegalovirus and epithelial tumors. EPCR is a major histocompatibility complex-like molecule that binds lipids analogously to the antigen-presenting molecule CD1d. However, the V(γ)4V(δ)5 TCR bound EPCR independently of lipids, in an antibody-like way. Moreover, the recognition of target cells by γδ T cells required a multimolecular stress signature composed of EPCR and costimulatory ligand(s). Our results demonstrate how a γδ TCR mediates recognition of broadly stressed human cells by engaging a stress-regulated self antigen.
Full text links
Publisher website (DOI) 10.1038/ni.2394
Europe PubMed Central 22885985
Pubmed 22885985
Keywords
Type of publication