Hwang SuJin, Palin Amy C, Li LiQi, Song Ki-Duk, Lee Jan, Herz Jasmin, Tubo Noah, Chu Hamlet, Pepper Marion, Lesourne Renaud, Zvezdova Ekaterina, Pinkhasov Julia, Jenkins Marc K, McGavern Dorian, Love Paul E
Program in Genomics of Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Room 2B-210, Building 6B, Bethesda, Maryland 20892, USA.
Viral Immunology and Intravital Imaging Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
Nat Commun. 2015 May 11;6:6982. doi: 10.1038/ncomms7982.
The T-cell antigen receptor (TCR) complex contains 10 copies of a di-tyrosine Immunoreceptor-Tyrosine-based-Activation-Motif (ITAM) that initiates TCR signalling by recruiting protein tyrosine kinases. ITAM multiplicity amplifies TCR signals, but the importance of this capability for T-cell responses remains undefined. Most TCR ITAMs (6 of 10) are contributed by the CD3ζ subunits. We generated 'knock-in' mice that express non-signalling CD3ζ chains in lieu of wild-type CD3ζ. Here we demonstrate that ITAM multiplicity is important for the development of innate-like T-cells and follicular helper T-cells, events that are known to require strong/sustained TCR-ligand interactions, but is not essential for 'general' T-cell responses including proliferation and cytokine production or for the generation of a diverse antigen-reactive TCR repertoire.
T细胞抗原受体（TCR）复合物包含10个二酪氨酸免疫受体酪氨酸激活基序（ITAM）拷贝，这些基序通过招募蛋白酪氨酸激酶来启动TCR信号传导。ITAM的多重性放大了TCR信号，但这种能力对T细胞反应的重要性仍不明确。大多数TCR ITAM（10个中的6个）由CD3ζ亚基提供。我们生成了“敲入”小鼠，其表达无信号传导功能的CD3ζ链以替代野生型CD3ζ。在此我们证明，ITAM的多重性对于先天样T细胞和滤泡辅助性T细胞的发育很重要，已知这些过程需要强烈/持续的TCR-配体相互作用，但对于包括增殖和细胞因子产生在内的“一般”T细胞反应或多样化抗原反应性TCR库的产生并非必不可少。
