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Elusive role of the CD94/NKG2C NK cell receptor in the response to cytomegalovirus: Novel experimental observations in a reporter cell system

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dc.contributor.author Pupuleku, Aldi, 1985-
dc.contributor.author Costa-García, Marcel
dc.contributor.author Farré, Domènec
dc.contributor.author Hengel, Hartmut
dc.contributor.author Angulo Aguado, Ana
dc.contributor.author Muntasell i Castellví, Aura, 1972-
dc.contributor.author López-Botet, Miguel
dc.date.accessioned 2018-03-08T09:17:55Z
dc.date.available 2018-03-08T09:17:55Z
dc.date.issued 2017
dc.identifier.citation Pupuleku A, Costa-García M, Farré D, Hengel H, Angulo A, Muntasell A et al. Elusive role of the CD94/NKG2C NK cell receptor in the response to cytomegalovirus: Novel experimental observations in a reporter cell system. Front Immunol. 2017 Oct 24;8:1317. DOI: 10.3389/fimmu.2017.01317
dc.identifier.issn 1664-3224
dc.identifier.uri http://hdl.handle.net/10230/34068
dc.description.abstract Human cytomegalovirus (HCMV) infection promotes the differentiation and persistent expansion of a mature NK cell subset, which displays high surface levels of the activating CD94/NKG2C NK cell receptor, together with additional distinctive phenotypic and functional features. The mechanisms underlying the development of adaptive NK cells remain uncertain but some observations support the involvement of a cognate interaction of CD94/NKG2C with ligand(s) displayed by HCMV-infected cells. To approach this issue, the heterodimer and its adaptor (DAP12) were expressed in the human Jurkat leukemia T cell line; signaling was detected by transfection of a reporter plasmid encoding for Luciferase (Luc) under NFAT/AP1-dependent control. Engagement of the receptor by solid-phase bound CD94- or NKG2C-specific monoclonal antibodies (mAbs) triggered Luc expression. Moreover, reporter activation was detectable upon interaction with HLA-E+ 721.221 (.221-AEH) cells, as well as with 721.221 cells incubated with synthetic peptides, which stabilized surface expression of endogenous HLA-E; the response was specifically antagonized by soluble NKG2C- and HLA-E-specific mAbs. By contrast, activation of Jurkat-NKG2C+ was undetectable upon interaction with Human Fetal Foreskin Fibroblasts (HFFF) infected with HCMV laboratory strains (i.e., AD169, Towne), regardless of their differential ability to preserve surface HLA-E expression. On the other hand, infection with two clinical isolates or with the endotheliotropic TB40/E strain triggered Jurkat-NKG2C+ activation; yet, this response was not inhibited by blocking mAbs and was independent of CD94/NKG2C expression. The results are discussed in the framework of previous observations supporting the hypothetical existence of specific ligand(s) for CD94/NKG2C in HCMV-infected cells.
dc.description.sponsorship The authors are supported by grants from: Plan Estatal I + D Retos (SAF2013-49063-C2-1-R; SAF2016-0363-C2-1-R), Spanish Ministry of Economy and Competitiveness (MINECO, FEDER); EU FP7-MINECO Infect-ERA program (PCIN-2015-191-C02-01); AP is supported by EU-FP7 Marie Curie Training Network (NATURIMMUN FP7-PEOPLE-2012-ITN-317013); HH is supported by Infect-ERA grant BMBF 031L0090; AA is supported by Plan Estatal I+D Retos grant SAF2014-55683, MINECO, FEDER.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Frontiers
dc.relation.ispartof Frontiers in Immunology. 2017 Oct 24;8:1317
dc.rights © 2017 Pupuleku, Costa-García, Farré, Hengel, Angulo, Muntasell and López-Botet. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (http://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.title Elusive role of the CD94/NKG2C NK cell receptor in the response to cytomegalovirus: Novel experimental observations in a reporter cell system
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.3389/fimmu.2017.01317
dc.subject.keyword CD94
dc.subject.keyword HLA-E
dc.subject.keyword NKG2C
dc.subject.keyword UL40
dc.subject.keyword Cytomegalovirus
dc.subject.keyword Natural killer cell
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/317013
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2013-49063-C2-1-R
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2016-0363-C2-1-R
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2014-55683
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/PCIN-2015-191-C02-01
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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