CD2 and CD3 associate independently with CD5 and differentially regulate signaling through CD5 in Jurkat T cells.
In T lymphocytes, the CD2 and CD5 glycoproteins are believed to be involved in the regulation of signals elicited by the TCR/CD3 complex. Here we show that CD2 and CD3 independently associate with CD5 in human PBMC and Jurkat cells. CD5 coprecipitates with CD2 in CD3-deficient cells and, conversely, coprecipitates ... with CD3 in cells devoid of CD2. In unstimulated CD2+ CD3+ Jurkat cells, CD5 associates equivalently with CD2 and CD3 and is as efficiently phosphorylated in CD2 as in CD3 immune complexes. However, upon activation the involvement of CD5 is the opposite in the CD2 and CD3 pathways. CD5 becomes rapidly tyrosine phosphorylated after CD3 stimulation, but is dephosphorylated upon CD2 cross-linking. These opposing effects correlate with the decrease in the activity of the SH2 domain-containing protein phosphatase 1 (SHP-1) following CD3 activation vs an enhanced activity of the phosphatase after CD2 triggering. The failure of CD5 to become phosphorylated on tyrosine residues in the CD2 pathway has no parallel with the lack of use of zeta-chains in CD2 signaling; contrasting with comparable levels of association of CD2 or CD3 with CD5, zeta associates with CD2 only residually and is nevertheless slightly phosphorylated after CD2 stimulation. The modulation of CD5 phosphorylation may thus represent a level of regulation controlled by CD2 in signal transduction mechanisms in human T lymphocytes.
Mesh Terms:
Antibodies, Monoclonal, Antigen-Antibody Complex, Antigens, CD2, Antigens, CD3, Antigens, CD5, Cells, Cultured, Enzyme Activation, Humans, Intracellular Signaling Peptides and Proteins, Jurkat Cells, Muromonab-CD3, Phosphorylation, Protein Phosphatase 1, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Protein Tyrosine Phosphatase, Non-Receptor Type 6, Protein Tyrosine Phosphatases, Protein-Serine-Threonine Kinases, SH2 Domain-Containing Protein Tyrosine Phosphatases, Signal Transduction, T-Lymphocytes, src Homology Domains
Antibodies, Monoclonal, Antigen-Antibody Complex, Antigens, CD2, Antigens, CD3, Antigens, CD5, Cells, Cultured, Enzyme Activation, Humans, Intracellular Signaling Peptides and Proteins, Jurkat Cells, Muromonab-CD3, Phosphorylation, Protein Phosphatase 1, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Protein Tyrosine Phosphatase, Non-Receptor Type 6, Protein Tyrosine Phosphatases, Protein-Serine-Threonine Kinases, SH2 Domain-Containing Protein Tyrosine Phosphatases, Signal Transduction, T-Lymphocytes, src Homology Domains
J. Immunol.
Date: Oct. 15, 1999
PubMed ID: 10510361
View in: Pubmed Google Scholar
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