title: Sensing of cell stress by human γδ TCR-dependent recognition of annexin A2.
abstract: Human γδ T cells comprise a first line of defense through T-cell receptor (TCR) recognition of stressed cells. However, the molecular determinants and stress pathways involved in this recognition are largely unknown. Here we show that exposure of tumor cells to various stress situations led to tumor cell recognition by a Vγ8Vδ3 TCR. Using a strategy that we previously developed to identify antigenic ligands of γδ TCRs, annexin A2 was identified as the direct ligand of Vγ8Vδ3 TCR, and was found to be expressed on tumor cells upon the stress situations tested in a reactive oxygen species-dependent manner. Moreover, purified annexin A2 was able to stimulate the proliferation of a Vδ2negγδ T-cell subset within peripheral blood mononuclear cells and other annexin A2-specific Vδ2negγδ T-cell clones could be derived from peripheral blood mononuclear cells. We thus propose membrane exposure of annexin A2 as an oxidative stress signal for some Vδ2negγδ T cells that could be involved in an adaptive stress surveillance.
authors.affiliation: ImmunoConcept, CNRS UMR 5164, University of Bordeaux, F-33000 Bordeaux, France.
authors.forename: Romain
authors.identifier: 0000-0001-8932-0171
authors.initials: R
authors.lastname: Marlin
authors.affiliation: ImmunoConcept, CNRS UMR 5164, University of Bordeaux, F-33000 Bordeaux, France.
authors.forename: Angela
authors.initials: A
authors.lastname: Pappalardo
authors.affiliation: ImmunoConcept, CNRS UMR 5164, University of Bordeaux, F-33000 Bordeaux, France.|Renal Transplantation Department, University Hospital of Bordeaux, F-33000 Bordeaux, France.
authors.forename: Hannah
authors.initials: H
authors.lastname: Kaminski
authors.affiliation: Cancer Immunology and Immunotherapy Centre, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, United Kingdom.
authors.forename: Carrie R
authors.initials: CR
authors.lastname: Willcox
authors.affiliation: ImmunoConcept, CNRS UMR 5164, University of Bordeaux, F-33000 Bordeaux, France.|Flow Cytometry Facility, TransBioMed Core, CNRS UMS 3427, INSERM US 005, University of Bordeaux, F-33000 Bordeaux, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Pitard
authors.affiliation: ImmunoConcept, CNRS UMR 5164, University of Bordeaux, F-33000 Bordeaux, France.
authors.forename: Sonia
authors.initials: S
authors.lastname: Netzer
authors.affiliation: ImmunoConcept, CNRS UMR 5164, University of Bordeaux, F-33000 Bordeaux, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Khairallah
authors.affiliation: Proteomic Facility, Functional Genomic Center, University of Bordeaux, Bordeaux F-33000, France.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Lomenech
authors.affiliation: ImmunoConcept, CNRS UMR 5164, University of Bordeaux, F-33000 Bordeaux, France.|INSERM, U892, Center of Research in Cancerology, Institute for Therapeutic Research at the University of Nantes, F-44000 Nantes, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Harly
authors.affiliation: INSERM, U892, Center of Research in Cancerology, Institute for Therapeutic Research at the University of Nantes, F-44000 Nantes, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Bonneville
authors.affiliation: ImmunoConcept, CNRS UMR 5164, University of Bordeaux, F-33000 Bordeaux, France.|Immunology and Immunogenetic laboratory, University Hospital of Bordeaux, F-33000 Bordeaux, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Moreau
authors.affiliation: INSERM, U892, Center of Research in Cancerology, Institute for Therapeutic Research at the University of Nantes, F-44000 Nantes, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Scotet
authors.affiliation: Cancer Immunology and Immunotherapy Centre, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, United Kingdom.
authors.forename: Benjamin E
authors.initials: BE
authors.lastname: Willcox
authors.affiliation: ImmunoConcept, CNRS UMR 5164, University of Bordeaux, F-33000 Bordeaux, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Faustin
authors.affiliation: ImmunoConcept, CNRS UMR 5164, University of Bordeaux, F-33000 Bordeaux, France; Julie.dechanet-merville@u-bordeaux.fr.|Flow Cytometry Facility, TransBioMed Core, CNRS UMS 3427, INSERM US 005, University of Bordeaux, F-33000 Bordeaux, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Déchanet-Merville
mesh_terms: D017306:Annexin A2 / Q000378:metabolism*; D019138:Antibodies, Blocking / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D045744:Cell Line, Tumor; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D008024:Ligands; D008213:Lymphocyte Activation; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism; D018384:Oxidative Stress; D011485:Protein Binding; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction; D013312:Stress, Physiological; D016176:T-Lymphocyte Subsets / Q000378:metabolism*
chemical_list: D017306:Annexin A2; D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D008024:Ligands; D016692:Receptors, Antigen, T-Cell, gamma-delta
keywords: cell stress surveillance; cytomegalovirus; gamma-delta T cells; innate-like lymphocytes; tumor immunology