首页> 美国卫生研究院文献>Proceedings of the National Academy of Sciences of the United States of America >Ly-6C regulates endothelial adhesion and homing of CD8+ T cells by activating integrin-dependent adhesion pathways
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Ly-6C regulates endothelial adhesion and homing of CD8+ T cells by activating integrin-dependent adhesion pathways

机译:Ly-6C通过激活整合素依赖性粘附途径来调节CD8 + T细胞的内皮粘附和归巢

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摘要

Ly-6C belongs to the Ly-6 family of glycosyl phosphatidylinositol-anchored surface glycoproteins and is expressed on a subset of mature CD8+ T cells. Ly-6C ligation can mediate T cell activation and causes interleukin 2 secretion in cytolytic T cell clones. We characterize herein a new mAb 1G7.G10 against Ly-6C that recognizes an epitope involved in lymphocyte adhesion and in lymphocyte homing. Pretreatment of lymph node lymphocytes and of purified CD8+ T cells (but not of lymphocytes depleted of CD8+ T cells) with 1G7.G10 reduced their in vitro binding to lymph node high endothelial venules by 28% and 34%, respectively. This effect was bypassed by cross-linking Ly-6C molecules with 1G7.G10 and a second-step antibody. The in vivo homing of (donor) CD8+ T lymphocytes to lymph nodes was reduced by Ly-6C blocking with 1G7.G10 (whole antibody) or with its fragments [F(ab) or F(ab)2] by 20% or by 32% and 48%, respectively. Cross-linking of Ly-6C in vitro induced very late antigen-4 and lymphocyte function-associated antigen 1-mediated aggregation of CD8+ T cells, suggesting that ligand binding to Ly-6C leads to activation of integrins. This activation may facilitate homing of Ly-6C+ CD8+ T cells in vivo.
机译:Ly-6C属于糖基磷脂酰肌醇固定的表面糖蛋白的Ly-6家族,在成熟的CD8 + T细胞的一部分上表达。 Ly-6C连接可以介导T细胞活化,并引起溶细胞性T细胞克隆中白介素2的分泌。我们在本文中表征了针对Ly-6C的新型mAb 1G7.G10,该抗体可识别参与淋巴细胞粘附和淋巴细胞归巢的表位。用1G7预处理淋巴结淋巴细胞和纯化的CD8 + T细胞(但不消耗CD8 + T细胞的淋巴细胞),G10降低了它们与淋巴结的体外结合高内皮小静脉分别增加28%和34%。通过将Ly-6C分子与1G7.G10和第二步抗体交联来绕过此作用。通过用1G7.G10(全抗体)或其片段[F(ab)或F(ab)进行Ly-6C阻断,减少了(供体)CD8 + T淋巴细胞在体内的归巢)2]分别减少20%或32%和48%。 Ly-6C的体外交联诱导CD4 + T细胞的抗原4和淋巴细胞功能相关的抗原1介导的聚集很晚,提示配体与Ly-6C的结合导致激活整联蛋白。该激活可能促进Ly-6C + CD8 + T细胞在体内的归巢。

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