Bettini Matthew L, Chou Po-Chein, Guy Clifford S, Lee Thomas, Vignali Kate M, Vignali Dario A A
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105;
Section of Diabetes and Endocrinology, Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston, TX 77030.
J Immunol. 2017 Sep 1;199(5):1555-1560. doi: 10.4049/jimmunol.1700069. Epub 2017 Jul 21.
For the αβ or γδTCR chains to integrate extracellular stimuli into the appropriate intracellular cellular response, they must use the 10 ITAMs found within the CD3 subunits (CD3γε, CD3δε, and ζζ) of the TCR signaling complex. However, it remains unclear whether each specific ITAM sequence of the individual subunit (γεδζ) is required for thymocyte development or whether any particular CD3 ITAM motif is sufficient. In this article, we show that mice utilizing a single ITAM sequence (γ, ε, δ, ζa, ζb, or ζc) at each of the 10 ITAM locations exhibit a substantial reduction in thymic cellularity and limited CD4CD8 (double-negative) to CD4CD8 (double-positive) maturation because of low TCR expression and signaling. Together, the data suggest that ITAM sequence diversity is required for optimal TCR signal transduction and subsequent T cell maturation.
为了使αβ或γδTCR链将细胞外刺激整合到适当的细胞内反应中，它们必须利用TCR信号复合物的CD3亚基（CD3γε、CD3δε和ζζ）中的10个免疫受体酪氨酸活化基序（ITAM）。然而，目前尚不清楚单个亚基（γεδζ）的每个特定ITAM序列对于胸腺细胞发育是否必需，或者任何特定的CD3 ITAM基序是否足够。在本文中，我们表明，在10个ITAM位置的每一个位置利用单个ITAM序列（γ、ε、δ、ζa、ζb或ζc）的小鼠，由于TCR表达和信号传导较低，胸腺细胞数量大幅减少，并且从CD4CD8（双阴性）到CD4CD8（双阳性）的成熟受到限制。总之，数据表明ITAM序列多样性是最佳TCR信号转导和随后T细胞成熟所必需的。
