Defined alphabeta T cell receptors with distinct ligand specificities do not require those ligands to signal double negative thymocyte differentiation.
Defined alphabeta T cell receptors with distinct ligand specificities do not require those ligands to signal double negative thymocyte differentiation.
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DOI：
10.1084/jem.20032204
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发表时间：
2004-06-21
期刊：
影响因子：
--
通讯作者：
Singer A
中科院分区：
文献类型：
--
作者：
Erman B;Guinter TI;Singer A
在胸腺中 T 细胞发育过程中，前 T 细胞受体 (TCR) 复合物向 CD4− CD8−（双阴性 [DN]）胸腺细胞发出信号，使其分化为 CD4+ CD8+（双阳性 [DP]）胸腺细胞，并且它们在没有明显配体结合的情况下产生此类信号。尽管不依赖于配体的信号传导并不常见，并且可能是前 TCR 所独有的，但其他 TCR 复合物（例如 αβ TCR 或 αγ TCR）如果在 DN 胸腺细胞上表达，也可能在没有配体参与的情况下向 DN 向 DP 转变发出信号。尽管 αγ TCR 复合物有效地向 DN 胸腺细胞分化发出信号，但尚不确定 αβ TCR 复合物是否也能够向 DN 胸腺细胞分化发出信号，也不确定这种信号是否依赖于配体接合。本研究通过在重组激活基因 2−/− pre-Tα−/− 双缺陷小鼠中表达定义的 αβ TCR 转基因来解决这些问题。在这种双缺陷小鼠中，唯一可以表达的抗原受体是由 αβ TCR 转基因编码的抗原受体。通过这种方式，本研究明确证明 αβ TCR 实际上可以发出 DN 到 DP 转变的信号。此外，这项研究表明，即使在缺乏特定 MHC 肽配体的情况下，转基因 αβ TCR 也会发出 DN 向 DP 转变的信号。
During T cell development in the thymus, pre–T cell receptor (TCR) complexes signal CD4− CD8− (double negative [DN]) thymocytes to differentiate into CD4+ CD8+ (double positive [DP]) thymocytes, and they generate such signals without apparent ligand engagements. Although ligand-independent signaling is unusual and might be unique to the pre-TCR, it is possible that other TCR complexes such as αβ TCR or αγ TCR might also be able to signal the DN to DP transition in the absence of ligand engagement if they were expressed on DN thymocytes. Although αγ TCR complexes efficiently signal DN thymocyte differentiation, it is not yet certain if αβ TCR complexes are also capable of signaling DN thymocyte differentiation, nor is it certain if such signaling is dependent upon ligand engagement. This study has addressed these questions by expressing defined αβ TCR transgenes in recombination activating gene 2−/− pre-Tα−/− double deficient mice. In such double deficient mice, the only antigen receptors that can be expressed are those encoded by the αβ TCR transgenes. In this way, this study definitively demonstrates that αβ TCR can in fact signal the DN to DP transition. In addition, this study demonstrates that transgenic αβ TCRs signal the DN to DP transition even in the absence of their specific MHC–peptide ligands.
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DOI：
10.1084/jem.192.4.537
发表时间：
2000-08-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Terrence K;Pavlovich CP;Matechak EO;Fowlkes BJ
通讯作者：
Fowlkes BJ
影响因子：
56.9
作者：
GRUSBY, MJ;JOHNSON, RS;GLIMCHER, LH
通讯作者：
GLIMCHER, LH
影响因子：
4.4
作者：
Lacorazza, HD;Tucek-Szabo, C;Nikolich-Zugich, J
通讯作者：
Nikolich-Zugich, J
影响因子：
64.8
作者：
MOMBAERTS, P;CLARKE, AR;TONEGAWA, S
通讯作者：
TONEGAWA, S
影响因子：
15.3
作者：
Gibbons, D;Douglas, NC;Hayday, AC
通讯作者：
Hayday, AC