Cytomegalovirus and tumor stress surveillance by binding of a human γδ T cell antigen receptor to endothelial protein C receptor

TY - JOUR

T1 - Cytomegalovirus and tumor stress surveillance by binding of a human γδ T cell antigen receptor to endothelial protein C receptor

AU - Willcox, Carrie R.

AU - Pitard, Vincent

AU - Netzer, Sonia

AU - Couzi, Lionel

AU - Salim, Mahboob

AU - Silberzahn, Tobias

AU - Moreau, Jean-Francois

AU - Hayday, Adrian C.

AU - Willcox, Benjamin E.

AU - Dechanet-Merville, Julie

PY - 2012/9

Y1 - 2012/9

N2 - T cells bearing gamma delta T cell antigen receptors (TCRs) function in lymphoid stress surveillance. However, the contribution of gamma delta TCRs to such responses is unclear. Here we found that the TCR of a human V(gamma)4V(delta)5 clone directly bound endothelial protein C receptor (EPCR), which allowed gamma delta 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(gamma)4V(delta)5 TCR bound EPCR independently of lipids, in an antibody-like way. Moreover, the recognition of target cells by gamma delta T cells required a multimolecular stress signature composed of EPCR and costimulatory ligand(s). Our results demonstrate how a gamma delta TCR mediates recognition of broadly stressed human cells by engaging a stress-regulated self antigen.

AB - T cells bearing gamma delta T cell antigen receptors (TCRs) function in lymphoid stress surveillance. However, the contribution of gamma delta TCRs to such responses is unclear. Here we found that the TCR of a human V(gamma)4V(delta)5 clone directly bound endothelial protein C receptor (EPCR), which allowed gamma delta 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(gamma)4V(delta)5 TCR bound EPCR independently of lipids, in an antibody-like way. Moreover, the recognition of target cells by gamma delta T cells required a multimolecular stress signature composed of EPCR and costimulatory ligand(s). Our results demonstrate how a gamma delta TCR mediates recognition of broadly stressed human cells by engaging a stress-regulated self antigen.

U2 - 10.1038/ni.2394

DO - 10.1038/ni.2394

M3 - Article

SN - 1529-2908

VL - 13

SP - 872

EP - 879

JO - Nature Immunology

JF - Nature Immunology

IS - 9

ER -