| First Author | Kim HR | Year | 2011 |
| Journal | J Exp Med | Volume | 208 |
| Issue | 12 | Pages | 2545-60 |
| PubMed ID | 22084409 | Mgi Jnum | J:178612 |
| Mgi Id | MGI:5299365 | Doi | 10.1084/jem.20110853 |
| Citation | Kim HR, et al. (2011) IGSF4 is a novel TCR zeta-chain-interacting protein that enhances TCR-mediated signaling. J Exp Med 208(12):2545-60 |
| abstractText | Immunoglobulin superfamily member 4 (IGSF4) is a known ligand of CRTAM, a receptor expressed in activated NKT and CD8(+) T cells, but its function in T cell immunity has not been elucidated. In this study, we show that IGSF4 directly interacts with the T cell receptor (TCR) zeta-chain and enhances TCR signaling by enhancing zeta-chain phosphorylation. Ectopic overexpression of IGSF4 enhances TCR-mediated T cell activation. In contrast, IGSF4 knockdown shows a dramatic decrease in markers associated with T cell activation compared with those in control small interfering RNA. The transmembrane domain is essential for TCR zeta-chain association and clustering to the immunological synapse, and the ectodomain is associated with T cell interaction with antigen-presenting cells (APCs). IGSF4-deficient mice have impaired TCR-mediated thymocyte selection and maturation. Furthermore, these mice reveal attenuated effector T cell functions accompanied by defective TCR signaling. Collectively, the results indicate that IGSF4 plays a central role in T cell functioning by dual independent mechanisms, control of TCR signaling and control of T cell-APC interaction. |
