Crippling of CD3-zeta ITAMs does not impair T cell receptor signaling

Immunity. 1999 Apr;10(4):409-20. doi: 10.1016/s1074-7613(00)80041-2.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Differentiation, T-Lymphocyte / biosynthesis
  • Antigens, Differentiation, T-Lymphocyte / genetics
  • CD3 Complex / genetics*
  • Calcium / metabolism
  • Cell Differentiation / immunology
  • Cell Membrane / chemistry
  • Cell Membrane / metabolism
  • Cytokines / metabolism
  • Cytotoxicity, Immunologic
  • Down-Regulation / immunology
  • Fas Ligand Protein
  • Female
  • Ligands
  • Lymphocyte Activation / genetics
  • Male
  • Membrane Glycoproteins / biosynthesis
  • Membrane Glycoproteins / genetics
  • Mice
  • Mice, Transgenic
  • Mutagenesis, Site-Directed
  • Phosphorylation
  • Receptor-CD3 Complex, Antigen, T-Cell / chemistry
  • Receptor-CD3 Complex, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / antagonists & inhibitors
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / physiology*
  • Signal Transduction / genetics
  • Signal Transduction / immunology*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • T-Lymphocytes, Cytotoxic / immunology
  • Transduction, Genetic / immunology
  • Tyrosine / metabolism
  • fas Receptor / biosynthesis
  • fas Receptor / genetics

Substances

  • Antigens, Differentiation, T-Lymphocyte
  • CD3 Complex
  • Cytokines
  • Fas Ligand Protein
  • Fasl protein, mouse
  • Ligands
  • Membrane Glycoproteins
  • Receptor-CD3 Complex, Antigen, T-Cell
  • Receptors, Antigen, T-Cell
  • fas Receptor
  • Tyrosine
  • Calcium