title: Cytomegalovirus and tumor stress surveillance by binding of a human γδ T cell antigen receptor to endothelial protein C receptor.
abstract: 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.
authors.affiliation: Birmingham Cancer Research UK Cancer Centre, School of Cancer Sciences, University of Birmingham, Birmingham, UK.
authors.forename: Carrie R
authors.initials: CR
authors.lastname: Willcox
authors.forename: Vincent
authors.initials: V
authors.lastname: Pitard
authors.forename: Sonia
authors.initials: S
authors.lastname: Netzer
authors.forename: Lionel
authors.initials: L
authors.lastname: Couzi
authors.forename: Mahboob
authors.initials: M
authors.lastname: Salim
authors.forename: Tobias
authors.initials: T
authors.lastname: Silberzahn
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Moreau
authors.forename: Adrian C
authors.initials: AC
authors.lastname: Hayday
authors.forename: Benjamin E
authors.initials: BE
authors.lastname: Willcox
authors.forename: Julie
authors.initials: J
authors.lastname: Déchanet-Merville
mesh_terms: D015703:Antigens, CD / Q000276:immunology* / Q000378:metabolism; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000276:immunology*; D000074283:Endothelial Protein C Receptor; D006801:Humans; D015151:Immunoblotting; D007157:Immunologic Surveillance / Q000276:immunology*; D047468:Immunoprecipitation; D009375:Neoplasms, Glandular and Epithelial / Q000276:immunology*; D011485:Protein Binding; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000276:immunology* / Q000378:metabolism; D013312:Stress, Physiological / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D000074283:Endothelial Protein C Receptor; C478370:PROCR protein, human; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011956:Receptors, Cell Surface