Requirement for association of p56lck with CD4 in antigen-specific signal transduction in T cells.
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.
Glaichenhaus
N
N
Department of Molecular and Cell Biology, University of California, Berkeley 94720.
Shastri
N
N
Littman
D R
DR
Turner
J M
JM
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D015704:CD4 Antigens / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D016827:CD8 Antigens; D004252:DNA Mutational Analysis; D004705:Endocytosis; D008213:Lymphocyte Activation; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D015398:Signal Transduction; D014162:Transfection
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D015704:CD4 Antigens; D016827:CD8 Antigens; D046911:Macromolecular Substances; D011948:Receptors, Antigen, T-Cell; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)