Defective T-cell receptor signalling and positive selection of Vav-deficient CD4+ CD8+ thymocytes.

Fischer KD; Zmuldzinas A; Gardner S; Barbacid M; Bernstein A; Guidos C

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Defective T-cell receptor signalling and positive selection of Vav-deficient CD4+ CD8+ thymocytes.

机译：T细胞受体信号缺陷和Vav缺陷CD4 + CD8 +胸腺细胞的阳性选择。

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During lymphocyte development, cellular proliferation and positive and negative selection events ensure the production of T and B lymphocytes bearing highly diverse, but self-tolerant, repertoires of antigen receptors. These processes are initiated when engagement of growth-factor receptors, or the T and B lymphocyte antigen receptors, induces tyrosine phosphorylation of specific SH2- and SH3-domain-containing cytoplasmic proteins, including Vav. Here we show that vav-/- embryonic stem cells generate only limited numbers of immature and mature T and B lymphocytes in the RAG-2 blastocyst complementation assay. Furthermore, Vav-deficient T lymphocytes showed severely impaired antigen receptor signalling. Finally, we demonstrate that Vav-dependent signalling pathways regulate maturation, but not CD4/CD8 lineage commitment, during T-cell-receptor-mediated positive selection of immature CD4+ CD8+ precursors into mature CD4+ CD8- or CD4- CD8+ T cells.

机译：在淋巴细胞发育过程中，细胞增殖以及阳性和阴性选择事件可确保产生T和B淋巴细胞，这些T和B淋巴细胞带有高度多样化但自我容忍的抗原受体库。当生长因子受体或T和B淋巴细胞抗原受体的结合诱导特定的含有SH2和SH3结构域的胞质蛋白（包括Vav）的酪氨酸磷酸化时，就会启动这些过程。在这里，我们显示vav-/-胚胎干细胞在RAG-2胚泡互补测定中仅生成有限数量的未成熟和成熟的T和B淋巴细胞。此外，Vav缺陷型T淋巴细胞显示抗原受体信号转导严重受损。最后，我们证明了在未成熟的CD4 + CD8 +前体进入成熟CD4 + CD8-或CD4- CD8 + T细胞的T细胞受体介导的阳性选择过程中，Vav依赖的信号通路调节成熟，但不调节CD4 / CD8谱系的定向。

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来源
《Nature》 |1995年第6521期|P.474-477|共4页
作者
Fischer KD; Zmuldzinas A; Gardner S; Barbacid M; Bernstein A; Guidos C;
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作者单位

Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.;

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收录信息美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种 eng
中图分类自然科学总论;
关键词
B-Lymphocyte Subsets; Proto-Oncogene Proteins; Receptors; Antigen; T-Cell; B淋巴细胞亚群; 原癌基因蛋白质类; 受体; 抗原; T细胞; 信号传递; T淋巴细胞亚群;

机译：B-Lymphocyte Subsets;Proto-Oncogene Proteins;Receptors;Antigen;T-Cell;B淋巴细胞亚群;原癌基因蛋白质类;受体;抗原;T细胞;信号传递;T淋巴细胞亚群;

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1. Early molecular events induced by T cell receptor (TCR) signaling in immature CD4+ CD8+ thymocytes: increased synthesis of TCR-alpha protein is an early response to TCR signaling that compensates for TCR-alpha instability, improves TCR assembly, and parallels other indicators of positive selection. [J] . K P Kearse, Y Takahama, J A Punt, The Journal of Experomental Medicine . 1995,第1期

机译：T细胞受体（TCR）信号在未成熟的CD4 + CD8 +胸腺细胞中诱导的早期分子事件：TCR-α蛋白合成的增加是对TCR信号的早期反应，补偿了TCR-α的不稳定性，改善了TCR组装，并与其他阳性指标平行选择。
2. Transient overexpression of CD4 enhances allelic exclusion of T-cell receptor (TCR) alpha chains and promotes positive selection of class II-restricted TCR-transgenic thymocytes. [J] . Dembic Z, Munthe LA, Schenck K, Molecular Immunology . 1998,第1期

机译：CD4的瞬时过表达增强了T细胞受体（TCR）α链的等位基因排斥，并促进了II类限制性TCR转基因胸腺细胞的阳性选择。
3. Role of CD8beta domains in CD8 coreceptor function: importance for MHC I binding, signaling, and positive selection of CD8+ T cells in the thymus. [J] . Bosselut R, Kubo S, Guinter T, Immunity . 2000,第4期

机译：CD8beta域在CD8受体功能中的作用：对于MHC I结合，信号传导和在胸腺中CD8 + T细胞的阳性选择非常重要。
4. Changes in Cd4+ and Cd8+ T-Cell Subpopulations in Chickens Vaccinated with La Sota or V4 Strains of Ndv [C] . . 2005

机译：接种La Sota或Ndv V4株疫苗的鸡中Cd4 +和Cd8 + T细胞亚群的变化
5. Skin-homing molecule and chemokine receptor expression on herpesvirus-specific CD8+ T-cells [D] . Hensel, Michael T. 2010

机译：疱疹病毒特异性CD8 + T细胞上的皮肤归巢分子和趋化因子受体表达
6. Early molecular events induced by T cell receptor (TCR) signaling in immature CD4+ CD8+ thymocytes: increased synthesis of TCR-alpha protein is an early response to TCR signaling that compensates for TCR-alpha instability improves TCR assembly and parallels other indicators of positive selection [O] . 1995

机译：T细胞受体（TCR）信号在未成熟的CD4 + CD8 +胸腺细胞中诱导的早期分子事件：TCR-α蛋白合成的增加是对TCR信号的早期反应补偿了TCR-α的不稳定性改善了TCR组装并与其他阳性指标平行选择
7. Early molecular events induced by T cell receptor (TCR) signaling in immature CD4+ CD8+ thymocytes: increased synthesis of TCR-alpha protein is an early response to TCR signaling that compensates for TCR-alpha instability, improves TCR assembly, and parallels other indicators of positive selection [O] . 1995

机译：T细胞受体（TCR）信号在未成熟的CD4 + CD8 +胸腺细胞中诱导的早期分子事件：TCR-alpha蛋白的合成增加是对TCR信号的早期反应，补偿了TCR-alpha的不稳定性，改善了TCR组装，并与其他阳性指标平行选择

Defective T-cell receptor signalling and positive selection of Vav-deficient CD4+ CD8+ thymocytes.

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