Human CD3γ, but not CD3δ, haploinsufficiency differentially impairs γδ versus αβ surface TCR expression

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dc.contributor.authorMuñoz Ruiz, Miguel
dc.contributor.authorPérez Flores, Verónica
dc.contributor.authorGarcillán Goyoaga, Beatriz de
dc.contributor.authorGuardo, Alberto C
dc.contributor.authorMazariegos, Marina S
dc.contributor.authorTakada, Hidetoshi
dc.contributor.authorAllende Martínez, Luis Miguel
dc.contributor.authorKilic, Sara S
dc.contributor.authorSanal, Ozden
dc.contributor.authorRoifman, Chaim M
dc.contributor.authorLópez Granados, Eduardo
dc.contributor.authorRecio Hoyas, María José
dc.contributor.authorMartínez Naves, Eduardo
dc.contributor.authorFernández Malavé, Edgar
dc.contributor.authorRegueiro González-Barros, José Ramón
dc.date.accessioned2023-06-19T13:46:15Z
dc.date.available2023-06-19T13:46:15Z
dc.date.issued2013-01-21
dc.description.abstractBackground: The T cell antigen receptors (TCR) of αβ and γδ T lymphocytes are believed to assemble in a similar fashion in humans. Firstly, αβ or γδ TCR chains incorporatea CD3δε dimer, then a CD3γε dimer and finally a ζζ homodimer, resulting in TCR complexes with the same CD3 dimer stoichiometry. Partial reduction in the expression of the highly homologous CD3γ and CD3δ proteins would thus be expected to have a similar impact in the assembly and surface expression of both TCR isotypes. To test this hypothesis, we compared the surface TCR expression of primary αβ and γδ T cells from healthy donors carrying a single null or leaky mutation in CD3G (γ+/−) or CD3D (δ+/−, δ+/leaky) with that of normal controls. Results: Although the partial reduction in the intracellular availability of CD3γ or CD3δ proteins was comparable as a consequence of the mutations, surface TCR expression measured with anti-CD3ε antibodies was significantly more decreased in γδ than in αβ T lymphocytes in CD3γ+/− individuals, whereas CD3δ+/− and CD3δ+/leaky donors showed a similar decrease of surface TCR in both T cell lineages. Therefore, surface γδ TCR expression was more dependent on available CD3γ than surface αβ TCR expression. Conclusions: The results support the existence of differential structural constraints in the two human TCR isotypes regarding the incorporation of CD3γε and CD3δε dimers, as revealed by their discordant surface expression behaviour when confronted with reduced amounts of CD3γ, but not of the homologous CD3δ chain. A modified version of the prevailing TCR assembly model is proposed to accommodate these new data.
dc.description.departmentDepto. de Inmunología, Oftalmología y ORL
dc.description.facultyFac. de Medicina
dc.description.refereedTRUE
dc.description.sponsorshipMinisterio de Educación
dc.description.sponsorshipInstituto de Salud Carlos III (ISCIII)
dc.description.sponsorshipComunidad de Madrid
dc.description.sponsorshipFundación Lair
dc.description.sponsorshipInstituto de Investigación Hospital 12 de Octubre
dc.description.statuspub
dc.eprint.idhttps://eprints.ucm.es/id/eprint/69224
dc.identifier.doi10.1186/1471-2172-14-3
dc.identifier.issn1471-2172
dc.identifier.officialurlhttp://www.biomedcentral.com/1471-2172/14/3
dc.identifier.urihttps://hdl.handle.net/20.500.14352/34400
dc.issue.number3
dc.journal.titleBMC Immunology
dc.language.isoeng
dc.page.final7
dc.page.initial1
dc.publisherBioMed Central
dc.relation.projectID(BFU2005-01738/BMC and SAF2011-24235)
dc.relation.projectID(ISCIII PI080921, PI060057 and RIER RD08-0075-0002)
dc.relation.projectID(GR/SAL/0570/2004 and S2011/BMD-2316)
dc.rightsAtribución 3.0 España
dc.rights.accessRightsopen access
dc.rights.urihttps://creativecommons.org/licenses/by/3.0/es/
dc.subject.keywordT cells
dc.subject.keywordCD3
dc.subject.keywordHaploinsufficiency
dc.subject.ucmInmunología
dc.subject.unesco2412 Inmunología
dc.titleHuman CD3γ, but not CD3δ, haploinsufficiency differentially impairs γδ versus αβ surface TCR expression
dc.typejournal article
dc.volume.number14
dspace.entity.typePublication
relation.isAuthorOfPublicationae412778-589a-4a17-ae3e-63a0413a4b9d
relation.isAuthorOfPublicatione5d88590-7bbf-4d46-84aa-6f2d8c8a47ea
relation.isAuthorOfPublication436ddd6b-73c0-4f41-9d60-f15490326809
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relation.isAuthorOfPublicationf497ca90-fd08-440c-a7a2-abaa7dee0039
relation.isAuthorOfPublication.latestForDiscoveryae412778-589a-4a17-ae3e-63a0413a4b9d
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