Requirement for association of p56lck with CD4 in antigen-specific signal transduction in T cells

Cell. 1991 Feb 8;64(3):511-20. doi: 10.1016/0092-8674(91)90235-q.

Abstract

The T cell-specific transmembrane glycoprotein CD4 interacts with class II MHC molecules via its external domain and is associated with tyrosine kinase p56lck via a cysteine motif in its cytoplasmic domain. We have assessed the ability of CD4 to synergize with the antigen-specific T cell receptor (TCR) for induction of transmembrane signals that result in lymphokine production. Mutant CD4 molecules were introduced into T cells that lacked endogenous CD4 but expressed TCRs specific for lysozyme peptides or the superantigen SEA bound to Ab or Abm12 class II MHC molecules. With either ligand, T cell activation occurred only when CD4 was associated with p56lck. These results demonstrate that residues within the cytoplasmic domain of CD4 are required for its coreceptor function in TCR-mediated signal transduction and strongly support the notion that the association of CD4 with p56lck is critical in this process.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, CD / metabolism
  • Antigens, Differentiation, T-Lymphocyte / metabolism
  • CD4 Antigens / physiology*
  • CD4-Positive T-Lymphocytes / physiology*
  • CD8 Antigens
  • DNA Mutational Analysis
  • Endocytosis
  • Lymphocyte Activation*
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • Macromolecular Substances
  • Mice
  • Molecular Sequence Data
  • Protein-Tyrosine Kinases / physiology*
  • Receptors, Antigen, T-Cell / physiology
  • Signal Transduction
  • Transfection

Substances

  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD4 Antigens
  • CD8 Antigens
  • Macromolecular Substances
  • Receptors, Antigen, T-Cell
  • Protein-Tyrosine Kinases
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)