Co-stimulation of T cells with CD2 augments TCR-CD3-mediated activation of protein tyrosine kinase p72syk, resulting in increased tyrosine phosphorylation of adapter proteins, Shc and Cbl.
Complete T cell activation requires not only the first signal via TCR-CD3 engagement, but also a co-stimulatory signal through accessory receptors such as CD2, LFA-1 and CD28. However, the pathway of co-stimulatory signaling through accessory receptors is incompletely understood. We report here that CD2 provides a co-stimulus for activation of CD3-mediated syk/ZAP-70 family kinase, p72Syk (Syk), in Jurkat T cells. Although cross-linking of CD2 alone or any combination of CD2 with LFA-1alpha, LFA-1beta or CD28 did not induce tyrosine phosphorylation of Syk, co-cross-linking of CD2 with CD3 enhanced CD3-mediated tyrosine phosphorylation of Syk. Enhancement of tyrosine phosphorylation of Syk by CD2 co-stimulation was CD2 antibody concentration-dependent, and time course studies showed that CD2 co-stimulation enhanced Syk tyrosine phosphorylation by 30 s and through 5 min stimulation compared with the control. In vitro kinase assay revealed that co-cross-linking of CD2 with CD3 augmented Syk kinase activity using myelin basic protein as a substrate. Furthermore, CD2 co-stimulation with CD3 resulted in enhanced tyrosine phosphorylation of adapter proteins, such as Shc and Cbl, in an antibody concentration-dependent manner. Finally, CD2 provided a co-stimulatory signals for synthesis of IL-2 in Jurkat cells and phytohemagglutinin (PHA)-activated T cells and for proliferation of PHA-activated T cells. Taken together, these results indicate that CD2 is an important co-stimulatory receptor for CD3-mediated T cell activation and functions in concert with CD3.
Department of Medicine, Osaka Dental University, Japan.
H
H
Umehara
J Y
JY
Huang
T
T
Kono
F H
FH
Tabassam
T
T
Okazaki
S
S
Gouda
Y
Y
Nagano
E T
ET
Bloom
N
N
Domae
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D001426:Bacterial Proteins / Q000378:metabolism*; D018801:CD2 Antigens / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology*; D003087:Colicins; D004792:Enzyme Precursors / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D047908:Intracellular Signaling Peptides and Proteins; D019169:Jurkat Cells / Q000276:immunology; D008213:Lymphocyte Activation; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D000072377:Syk Kinase; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology*
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D001426:Bacterial Proteins; D018801:CD2 Antigens; D017252:CD3 Complex; D003087:Colicins; D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; C528024:SHC1 protein, human; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; C007104:colicin immunity proteins; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase