| First Author | Li D | Year | 2009 |
| Journal | J Biol Chem | Volume | 284 |
| Issue | 31 | Pages | 21001-10 |
| PubMed ID | 19483086 | Mgi Jnum | J:153186 |
| Mgi Id | MGI:4361108 | Doi | 10.1074/jbc.M109.002865 |
| Citation | Li D, et al. (2009) LFA-1 regulates CD8+ T cell activation via T cell receptor-mediated and LFA-1-mediated Erk1/2 signal pathways. J Biol Chem 284(31):21001-10 |
| abstractText | LFA-1 regulates T cell activation and signal transduction through the immunological synapse. T cell receptor (TCR) stimulation rapidly activates LFA-1, which provides unique LFA-1-dependent signals to promote T cell activation. However, the detailed molecular pathways that regulate these processes and the precise mechanism by which LFA-1 contributes to TCR activation remain unclear. We found LFA-1 directly participates in Erk1/2 signaling upon TCR stimulation in CD8+ T cells. The presence of LFA-1, not ligand binding, is required for the TCR-mediated Erk1/2 signal pathway. LFA-1-deficient T cells have defects in sustained Erk1/2 signaling and TCR/CD3 clustering, which subsequently prevents MTOC reorientation, cell cycle progression, and mitosis. LFA-1 regulates the TCR-mediated Erk1/2 signal pathway in the context of immunological synapse for recruitment and amplification of the Erk1/2 signal. In addition, LFA-1 ligation with ICAM-1 generates an additional Erk1/2 signal, which synergizes with the existing TCR-mediated Erk1/2 signal to enhance T cell activation. Thus, LFA-1 contributes to CD8+ T cell activation through two distinct signal pathways. We demonstrated that the function of LFA-1 is to enhance TCR signaling through the immunological synapse and deliver distinct signals in CD8+ T cell activation. |
