First Author | Yang H | Year | 2006 |
Journal | J Immunol | Volume | 176 |
Issue | 10 | Pages | 5898-907 |
PubMed ID | 16670297 | Mgi Jnum | J:131679 |
Mgi Id | MGI:3774201 | Doi | 10.4049/jimmunol.176.10.5898 |
Citation | Yang H, et al. (2006) CD2BP1 modulates CD2-dependent T cell activation via linkage to protein tyrosine phosphatase (PTP)-PEST. J Immunol 176(10):5898-907 |
abstractText | Human CD2 regulates T cell activation and adhesion via mechanisms yet to be fully understood. This study focuses on CD2BP1, a CD2 cytoplasmic tail-binding protein preferentially expressed in hematopoetic cells. Structural and functional analyses suggest that CD2BP1 acts as a scaffold protein, participating in regulation of the actin cytoskeleton. In this study, using a murine Ag-specific primary T cell transduction system to assess CD69, IL-2, and IFN-gamma expression, we provide evidence that CD2BP1 directly and negatively impacts T cell activation via isolated CD2 triggering or TCR stimulation dependent on coordinate CD2 engagement. Disruption of protein tyrosine phosphatase-PEST and/or CD2BP1 association with the CD2 signalsome rescues T cells from the inhibitory effect of CD2 crosslinking. The overexpression of CD2BP1 selectively attenuates phospholipase Cgamma1, ERK1/2, and p38 phosphorylation without abrogating CD2-independent TCR stimulation. This study provides new insight on the regulation of T cell activation and may have implications for autoimmune processes known to be associated with CD2BP1 mutations. |