title: CD3γ-independent pathways in TCR-mediated signaling in mature T and iNKT lymphocytes.
abstract: Antigen recognition by T-lymphocytes through the T-cell antigen receptor, TCR-CD3, is a central event in the initiation of an immune response. CD3 proteins may have redundant as well as specific contributions to the intracellular propagation of TCR-mediated signals. However, to date, the relative role that each CD3 chain plays in signaling is controversial. In order to examine the roles of CD3γ chain in TCR signaling, we analyzed proximal and distal signaling events in human CD3γ(-/-) primary and Herpesvirus saimiri (HVS)-transformed T cells. Following TCR-CD3 engagement, certain early TCR signaling pathways (ZAP-70, ERK, p38 and mTORC2 phosphorylation, and actin polymerization) were comparable with control HVS-transformed T cells. However, other signaling pathways were affected, such TCRζ phosphorylation, indicating that the CD3γ chain contributes to improve TCR signaling efficiency and survival. On the other hand, CD3γ(-/-) primary invariant NKT cells (iNKT cells) showed a normal expansion in response to alpha-galactosylceramide (α-GalCer) and TCRVβ11(bright) iNKT cells were preferentially selected in this in vitro culture system, perhaps as a consequence of selective events in the thymus. Our results collectively indicate that a TCR lacking CD3γ can propagate a number of signals through the remaining invariant chains, likely the homologous CD3δ chain, which replaces it at the mutant TCR.
authors.affiliation: Inmunología, Facultad de Medicina, Universidad Complutense, Madrid, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Reiné
authors.forename: Elena M
authors.initials: EM
authors.lastname: Busto
authors.forename: Miguel
authors.initials: M
authors.lastname: Muñoz-Ruiz
authors.forename: Nineth E
authors.initials: NE
authors.lastname: Rossi
authors.forename: José L
authors.initials: JL
authors.lastname: Rodríguez-Fernández
authors.forename: Eduardo
authors.initials: E
authors.lastname: Martínez-Naves
authors.forename: José R
authors.initials: JR
authors.lastname: Regueiro
authors.forename: María J
authors.initials: MJ
authors.lastname: Recio
mesh_terms: D000328:Adult; D000818:Animals; D017252:CD3 Complex / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002461:Cell Line, Transformed; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D005699:Galactosylceramides / Q000276:immunology / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism; D010766:Phosphorylation; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology* / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D055815:Young Adult
chemical_list: D017252:CD3 Complex; C452842:CD3 antigen, gamma chain; C121704:CD3 antigen, zeta chain; D005699:Galactosylceramides; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; C493154:alpha-galactosylceramide