| First Author | Wensveen FM | Year | 2010 |
| Journal | Immunity | Volume | 32 |
| Issue | 6 | Pages | 754-65 |
| PubMed ID | 20620942 | Mgi Jnum | J:162395 |
| Mgi Id | MGI:4818827 | Doi | 10.1016/j.immuni.2010.06.005 |
| Citation | Wensveen FM, et al. (2010) Apoptosis threshold set by Noxa and Mcl-1 after T cell activation regulates competitive selection of high-affinity clones. Immunity 32(6):754-65 |
| abstractText | The adaptive immune system generates protective T cell responses via a poorly understood selection mechanism that favors expansion of clones with optimal affinity for antigen. Here we showed that upon T cell activation, the proapoptotic molecule Noxa (encoded by Pmaip1) and its antagonist Mcl-1 were induced. During an acute immune response against influenza or ovalbumin, Pmaip1(-/-) effector T cells displayed decreased antigen affinity and functionality. Molecular analysis of influenza-specific T cells revealed persistence of many subdominant clones in the Pmaip1(-/-) effector pool. When competing for low-affinity antigen, Pmaip1(-/-) TCR transgenic T cells had a survival advantage in vitro, resulting in increased numbers of effector cells in vivo. Mcl-1 protein stability was controlled by T cell receptor (TCR) affinity-dependent interleukin-2 signaling. These results establish a role for apoptosis early during T cell expansion, based on antigen-driven competition and survival of the fittest T cells. |
