title: Crippling of CD3-zeta ITAMs does not impair T cell receptor signaling.
abstract: We evaluated the importance of CD3-zeta ITAMs in T cell responses by breeding the P14 transgenic TCR into mice in which CD3-zeta chains lacking all or part of their ITAMs were genetically substituted for wild-type CD3-zeta chains. In contrast to the H-Y TCR, the P14 TCR permitted the development of peripheral CD8+ T cells harboring signaling-defective CD3-zeta subunits. The absence of functional CD3-zeta ITAMs did not reduce the spectrum of activation events and effector functions that constitute the normal attributes of mature CD8+ T cells. The only detectable differences were quantitative and noted only when T cells were challenged with suboptimal peptide concentrations. Therefore, the ITAMs present in the CD3-gammadeltaepsilon module are sufficient for qualitatively normal TCR signaling and those present in CD3-zeta have no exclusive role during T cell activation.
authors.affiliation: Centre d'Immunologie, INSERM-CNRS de Marseille-Luminy, France.
authors.forename: L
authors.initials: L
authors.lastname: Ardouin
authors.forename: C
authors.initials: C
authors.lastname: Boyer
authors.forename: A
authors.initials: A
authors.lastname: Gillet
authors.forename: J
authors.initials: J
authors.lastname: Trucy
authors.forename: A M
authors.initials: AM
authors.lastname: Bernard
authors.forename: J
authors.initials: J
authors.lastname: Nunes
authors.forename: J
authors.initials: J
authors.lastname: Delon
authors.forename: A
authors.initials: A
authors.lastname: Trautmann
authors.forename: H T
authors.initials: HT
authors.lastname: He
authors.forename: B
authors.initials: B
authors.lastname: Malissen
authors.forename: M
authors.initials: M
authors.lastname: Malissen
mesh_terms: D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis / Q000235:genetics; D017252:CD3 Complex / Q000235:genetics*; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D015536:Down-Regulation / Q000276:immunology; D053222:Fas Ligand Protein; D005260:Female; D008024:Ligands; D008213:Lymphocyte Activation / Q000235:genetics; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000737:chemistry / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014161:Transduction, Genetic / Q000276:immunology; D014443:Tyrosine / Q000378:metabolism; D019014:fas Receptor / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D016207:Cytokines; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008024:Ligands; D008562:Membrane Glycoproteins; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011948:Receptors, Antigen, T-Cell; D019014:fas Receptor; D014443:Tyrosine; D002118:Calcium