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Kosugi, A. et al.

Kosugi, Saitoh, Noda, Miyake, Yamashita, Kimoto, Ogata, Hamaoka,

Physical and functional association between thymic shared antigen-1/stem cell antigen-2 and the T cell receptor complex.

Thymic shared antigen-1 (TSA-1)/stem cell Ag-2 ( Sca-2) is a glycosylphosphatidylinositol (GPI)-anchored antigen expressed on lymphocytes. We have previously demonstrated that a signal via TSA-1/ Sca-2 inhibits T cell receptor (TCR)-mediated T cell activation and apoptosis. To elucidate a molecular mechanism for TSA-1-mediated modulation of the TCR-signaling pathway, we examined whether TSA-1 is physically coupled to the TCR in the present study. TSA-1 was clearly associated with CD3zeta chains in T cell hybridomas, activated T cells, and COS-7 cells transfected with TSA-1 and CD3zeta cDNA. The physical association was confirmed on the surface of T cells in immunoprecipitation and confocal microscopy. The analysis using stable and transient transfectants expressing a transmembrane form of TSA-1 revealed that the association of CD3zeta did not require the GPI anchor of TSA-1. Finally, tyrosine phosphorylation of CD3zeta chains was induced after stimulation with anti-TSA-1, suggesting that a functional association between these two molecules also exists. These results imply that the physical association to CD3zeta underlies a regulatory role of TSA-1/ Sca-2 in the TCR-signaling pathway.[1]

References

Physical and functional association between thymic shared antigen-1/stem cell antigen-2 and the T cell receptor complex. Kosugi, A., Saitoh, S., Noda, S., Miyake, K., Yamashita, Y., Kimoto, M., Ogata, M., Hamaoka, T. J. Biol. Chem. (1998) [Pubmed]

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