Sensing cellular stress by human Gamma-Delta TCR

Abstract

Event Abstract Back to Event Sensing cellular stress by human Gamma-Delta TCR Romain Marlin1, Hannah Kaminski1, Sonia Netzer1, Vincent Pitard1, Christelle Harly1, Emmanuel Scotet2, Jean-Francois Moreau1, 3 and Julie Déchanet-Merville1* 1 UMR 5164 CIRID, France 2 CRCNA, INSERM UMR892, CNRS UMR6299, France 3 Immunology and Immunogenetic laboratory, France Human non-Vδ2γδ T cells constitute a first line of defence in epithelium and organs by recognizing modified cells as virus infected or transformed cells. This reactivity suggests recognition of stress-associated self-antigens by non-Vδ2 TCRs. In order to identify these uncharacterized antigens, we set up a strategy comprising mice immunization with tumor cells targeted by non-Vδ2 TCRs and selection of mAbs able to specifically abrogate the reactivity of γδ TCR transductants against these targets. In this study, we focused on a Vγ8Vδ3 TCR, which conferred to transductant a restricted reactivity against U373MG glioblastoma cell line. A blocking mAb (FMS-01) was generated against U373MG that specifically abrogated recognition by both Vγ8Vδ3 transductant and T cell clone, suggesting that FMS-01 mAb targets the antigenic ligand of Vγ8Vδ3 TCR. Surprisingly, we showed that modification of U373MG culture conditions as high level cell confluence, thermic choc, hypoxic stress or CMV infection, increased the reactivity of Vγ8Vδ3 transductant and T cell clone. These stress conditions were able to induce Vγ8Vδ3 transductant activation against other glioblastoma cell lines (U343MG and U251MG). This recognition of stressed cells was TCR dependent and blocked by FMS-01 mAb. Moreover, stress increased expression of FMS-01 targeted antigen that directly correlated with Vγ8Vδ3 transductant activation. Identification of FMS-01 targeted antigen is in process. In conclusion, our results show that stress conditions can induce the expression of γδ TCR antigens. Because these antigens are critical for γδ T cell recognition, their identification could lead to new immunotherapeutical treatments in cancer such as glioma. Keywords: gamma-delta T cells, Antigens, surveillance, Stress mechanics, Glioblastoma Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Innate immunity Citation: Marlin R, Kaminski H, Netzer S, Pitard V, Harly C, Scotet E, Moreau J and Déchanet-Merville J (2013). Sensing cellular stress by human Gamma-Delta TCR. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.01154 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 15 Jul 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Julie Déchanet-Merville, UMR 5164 CIRID, Bordeaux, France, jdechanet@immuconcept.org Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Romain Marlin Hannah Kaminski Sonia Netzer Vincent Pitard Christelle Harly Emmanuel Scotet Jean-Francois Moreau Julie Déchanet-Merville Google Romain Marlin Hannah Kaminski Sonia Netzer Vincent Pitard Christelle Harly Emmanuel Scotet Jean-Francois Moreau Julie Déchanet-Merville Google Scholar Romain Marlin Hannah Kaminski Sonia Netzer Vincent Pitard Christelle Harly Emmanuel Scotet Jean-Francois Moreau Julie Déchanet-Merville PubMed Romain Marlin Hannah Kaminski Sonia Netzer Vincent Pitard Christelle Harly Emmanuel Scotet Jean-Francois Moreau Julie Déchanet-Merville Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.