RT Journal Article
T1 The role of the different CD3γ domains in TCR expression and signaling
A1 Garcillán, Beatriz
A1 Megino, Rebeca F.
A1 Herrero Alonso, Marta
A1 Guardo, Alberto C.
A1 Pérez Flores, Verónica
A1 Martín Fernández, José M.
A1 Marín Marín, Ana Victoria
A1 Regueiro González-Barros, José Ramón
AB The CD3 subunits of the T-cell antigen receptor (TCR) play a central role in regulation of surface TCR expression levels. Humans who lack CD3γ (γ—) show reduced surface TCR expression levels and abolished phorbol ester (PMA)-induced TCR down-regulation. The response to PMA is mediated by a double leucine motif in the intracellular (IC) domain of CD3γ. However, the molecular cause of the reduced TCR surface expression in γ— lymphocytes is still not known. We used retroviral vectors carrying wild type CD3γ or CD3δ or the following chimeras (EC-extracellular, TM-transmembrane and IC): δECγTMγIC (δγγ for short), γγδ, γδδ and γγ-. Expression of γγγ, γγδ, γδδ or γγ- in the γ— T cell line JGN, which lacks surface TCR, demonstrated that cell surface TCR levels in JGN were dependent on the EC domain of CD3γ and could not be replaced by the one of CD3δ. In JGN and primary γ— patient T cells, the tested chimeras confirmed that the response to PMA maps to the IC domain of CD3γ. Since protein homology explains these results better than domain structure, we conclude that CD3γ contributes conformational cues that improve surface TCR expression, likely at the assembly or membrane transport steps. In JGN cells all chimeric TCRs were signalling competent. However, an IC domain at CD3γ was required for TCR-induced IL-2 and TNF-α production and CD69 expression, indicating that a TCR without a CD3γ IC domain has altered signalling capabilities.
PB Frontiers Media
YR 2022
FD 2022-09-02
LK https://hdl.handle.net/20.500.14352/106732
UL https://hdl.handle.net/20.500.14352/106732
LA eng
NO Garcillán B, Megino RF, Herrero-Alonso M, Guardo AC, Perez-Flores V, Juraske C, Idstein V, Martin-Fernandez JM, Geisler C, Schamel WWA, Marin AV and Regueiro JR (2022) The role of the different CD3γ domains in TCR expression and signaling. Front. Immunol. 13:978658. doi: 10.3389/fimmu.2022.978658
NO Ministerio de Economía y Competitividad (España)
NO Comunidad Autónoma de Madrid
NO Asociación Española Contra el Cáncer
DS Docta Complutense
RD 16 abr 2025