| First Author | Zhang J | Year | 2002 |
| Journal | J Immunol | Volume | 169 |
| Issue | 5 | Pages | 2236-40 |
| PubMed ID | 12193687 | Mgi Jnum | J:120676 |
| Mgi Id | MGI:3707641 | Doi | 10.4049/jimmunol.169.5.2236 |
| Citation | Zhang J, et al. (2002) Cutting edge: regulation of T cell activation threshold by CD28 costimulation through targeting Cbl-b for ubiquitination. J Immunol 169(5):2236-40 |
| abstractText | Optimal T cell activation requires signaling through the TCR and CD28 costimulatory receptor. CD28 costimulation is believed to set the threshold for T cell activation. Recently, Cbl-b, a ubiquitin ligase, has been shown to negatively regulate CD28-dependent T cell activation. In this report, we show that CD28 costimulation selectively induces greater ubiquitination and degradation of Cbl-b in wild-type T cells than CD3 stimulation alone, and TCR-induced Cbl-b ubiquitination and degradation are significantly reduced in CD28-deficient T cells. Stimulation of CD28-deficient T cells with higher doses of anti-CD3 results in increased ubiquitination of Cbl-b, which correlates with enhanced T cell responses. Our results demonstrate that CD28 costimulation regulates the threshold for T cell activation, at least in part, by promoting Cbl-b ubiquitination and degradation. |
