Crippling of CD3-zeta ITAMs does not impair T cell receptor signaling.
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.
Ardouin
L
L
Centre d'Immunologie, INSERM-CNRS de Marseille-Luminy, France.
Boyer
C
C
Gillet
A
A
Trucy
J
J
Bernard
A M
AM
Nunes
J
J
Delon
J
J
Trautmann
A
A
He
H T
HT
Malissen
B
B
Malissen
M
M
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
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