CD6 regulates T-cell responses through activation-dependent recruitment of the positive regulator SLP-76

Mol Cell Biol. 2006 Sep;26(17):6727-38. doi: 10.1128/MCB.00688-06.


Deciphering the role of lymphocyte membrane proteins depends on dissecting the role of a protein in the steady state and on engagement with its ligand. We show that expression of CD6 in T cells limits their responsiveness but that engagement by the physiological ligand CD166 gives costimulation. This costimulatory effect of CD6 is mediated through phosphorylation-dependent binding of a specific tyrosine residue, 662Y, in its cytoplasmic region to the adaptor SLP-76. A direct interaction between SLP-76 and CD6 was shown by binding both to a phosphorylated peptide (equilibrium dissociation constant [K(D)] = 0.5 muM at 37 degrees C) and, using a novel approach, to native phosphorylated CD6. Evidence that CD6 and SLP-76 interact in cells was obtained in coprecipitation experiments with normal human T cells. Analysis of human CD6 mutants in a murine T-cell hybridoma model showed that both costimulation by CD6 and the interaction between CD6 and SLP-76 were dependent on 662Y. The results have implications for regulation by CD6 and the related T-cell surface protein, CD5.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activated-Leukocyte Cell Adhesion Molecule / immunology
  • Adaptor Proteins, Signal Transducing
  • Animals
  • Antibodies, Monoclonal / immunology
  • Antigens, CD / chemistry
  • Antigens, CD / immunology*
  • Antigens, Differentiation, T-Lymphocyte / chemistry
  • Antigens, Differentiation, T-Lymphocyte / immunology*
  • CD5 Antigens / chemistry
  • Humans
  • Interleukin-2 / biosynthesis
  • Jurkat Cells
  • Lymphocyte Activation / immunology*
  • Mice
  • Peptides / metabolism
  • Phosphoproteins / metabolism*
  • Phosphorylation
  • Protein Binding
  • T-Lymphocytes / immunology*
  • src Homology Domains


  • Activated-Leukocyte Cell Adhesion Molecule
  • Adaptor Proteins, Signal Transducing
  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD5 Antigens
  • CD6 antigen
  • Interleukin-2
  • Peptides
  • Phosphoproteins
  • SLP-76 signal Transducing adaptor proteins