Key role of Free Heavy Chain of HLA class I molecules in HCMV and tumor stress sensing by gamma-delta TCR

Abstract

Event Abstract Back to Event Key role of Free Heavy Chain of HLA class I molecules in HCMV and tumor stress sensing by gamma-delta TCR Romain Marlin1, Sonia Netzer1, Vincent Pitard1, Sophie Daburon1, Christelle Harly1, Thomas Bachelet1, Jean-François Moreau1, 2, Jean-Luc Taupin1, 2 and Julie Dechanet1* 1 UMR 5164 CIRID, Univ. Bordeaux Segalen - CNRS, France 2 Immunology and Immunogenetic laboratory, France Non-Vδ2 γδ T cell clones isolated from Cytomegalovirus (HCMV)-infected individuals show dual TCR dependent reactivity against tumor cell lines and HCMV-infected cells suggesting recognition of stress-associated self antigens by non-Vδ2 TCRs. In order to identify these uncharacterized ligands, we immunize mice with tumor cells targeted by HCMV-reactive non-Vδ2 TCRs and select mAbs able to specifically abrogate the reactivity of γδ TCR transductants against these targets. In this study, we focused on a Vγ9Vδ3 TCR, which confers to transductants a restricted reactivity against three tumor B cell lines only. By contrast, several blocking mAbs (LSM) selected to recognize Vγ9Vδ3 antigen, ubiquitously targeted HLA class I (HLA-I) molecules expressed by a wide panel of cells. These results suggested the Vγ9Vδ3 TCR recognition of HLA-I molecules expressed in a particular shape or environment in the three B cell targets. Interestingly, B cell targets and HCMV-infected cells expressed β-2-microglobulin-free HLA-I heavy chains (FHC). Silencing β-2-microglobulin in B cell targets abrogated both HLA-I FHC cell surface expression and Vγ9Vδ3 TCR reactivity, suggesting the recognition of HLA-I FHC by the Vγ9Vδ3 TCR. Moreover, the original Vγ9Vδ3 T clone expressed CD85j and CD158b inhibitory receptors specific for HLA-I, that do not bind FHC, suggesting a regulation of TCR-mediated HLA-I recognition in physiological context. Blocking these receptors markedly increased the Vγ9Vδ3 T clone reactivity against B cell targets and HCMV-infected cells. Altogether, our results identify HLA-I FHC as a potential stress-associated antigen common to HCMV-infection or cellular transformation that mediate stress surveillance by γδ T cells. Keywords: gamma-delta T cells, HLA Antigens, ligand-receptor interaction, CMV, B cells Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Innate immunity Citation: Marlin R, Netzer S, Pitard V, Daburon S, Harly C, Bachelet T, Moreau J, Taupin J and Dechanet J (2013). Key role of Free Heavy Chain of HLA class I molecules in HCMV and tumor stress sensing by gamma-delta TCR . Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00960 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: 25 Jun 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Julie Dechanet, UMR 5164 CIRID, Univ. Bordeaux Segalen - CNRS, Bordeaux, France, jdechanet@cirid.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 Sonia Netzer Vincent Pitard Sophie Daburon Christelle Harly Thomas Bachelet Jean-François Moreau Jean-Luc Taupin Julie Dechanet Google Romain Marlin Sonia Netzer Vincent Pitard Sophie Daburon Christelle Harly Thomas Bachelet Jean-François Moreau Jean-Luc Taupin Julie Dechanet Google Scholar Romain Marlin Sonia Netzer Vincent Pitard Sophie Daburon Christelle Harly Thomas Bachelet Jean-François Moreau Jean-Luc Taupin Julie Dechanet PubMed Romain Marlin Sonia Netzer Vincent Pitard Sophie Daburon Christelle Harly Thomas Bachelet Jean-François Moreau Jean-Luc Taupin Julie Dechanet 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.