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一种由自然杀伤细胞和T细胞受体γ/δ+ T淋巴细胞表达的新型功能性细胞表面二聚体(Kp43)。I. 抗Kp43单克隆抗体对白细胞介素-2依赖性增殖的抑制作用。

A novel functional cell surface dimer (Kp43) expressed by natural killer cells and T cell receptor-gamma/delta+ T lymphocytes. I. Inhibition of the IL-2-dependent proliferation by anti-Kp43 monoclonal antibody.

作者信息

Aramburu J, Balboa M A, Ramírez A, Silva A, Acevedo A, Sánchez-Madrid F, De Landázuri M O, López-Botet M

机构信息

Sección de Immunología y Servicio de Anatomía Patológica, Hospital de la Princesa, Madrid, Spain.

出版信息

J Immunol. 1990 Apr 15;144(8):3238-47.

PMID:1691231
Abstract

In the present study we describe a novel functional cell surface molecule, designated as Kp43, which is expressed among leukocytes by NK cells, TCR-gamma/delta + T lymphocytes, and some CD8+ CD56+TCR-alpha/beta + T cell clones. The Kp43 Ag is a 70-kDa disulfide-linked dimer, which migrates in SDS-PAGE under reducing conditions as a single 43-kDa band. Two-color immunofluorescence staining of fresh PBL revealed that only a fraction of CD16+, and of TCR-gamma/delta + T lymphocytes expressed the Ag. The analysis of TCR-alpha/beta + T cell clones showed that a small proportion (2 out of 20) weakly expressed Kp43 together with the CD8 and CD56 molecules. By immunoperoxidase staining of different tissues the anti-Kp43, reactivity was detected exclusively in lymphoid organs, where a minority of scattered cells was stained, and in some liver sinusoidal cells. Essentially all NK cells acquired Kp43 when stimulated with a B lymphoblastoid cell line. By contrast, the pattern of distribution of Kp43 remained stable upon in vitro culture of T-gamma/delta lymphocytes, thus delineating two subsets according to its expression. In lymphokine-activated killer populations, obtained by culturing either PBL or NK cells with high concentration of IL-2, most CD16+ and CD56+ cells became Kp43+. The Kp43-specific mAb inhibited the IL-2-dependent proliferative response of cultured NK and TCR-gamma/delta + T cells without affecting their non-MHC-restricted cytotoxicity. The partial inhibitory effect, which was mediated as well by pepsin digested F(ab')2 fragments, was lost upon reduction to Fab. The anti-Kp43 mAb did not interfere with the specific binding of IL-2 to its surface receptors. Altogether the data point out that the Kp43 dimer is involved in the regulation of the IL-2-dependent proliferative response of NK cells and a subset of TCR-gamma/delta + T lymphocytes.

摘要

在本研究中,我们描述了一种新型功能性细胞表面分子,命名为Kp43,它在白细胞中由自然杀伤细胞(NK细胞)、TCR-γ/δ + T淋巴细胞以及一些CD8 + CD56 + TCR-α/β + T细胞克隆表达。Kp43抗原是一种70 kDa的二硫键连接的二聚体,在还原条件下于SDS-PAGE中迁移为单一的43 kDa条带。新鲜外周血淋巴细胞(PBL)的双色免疫荧光染色显示,只有一部分CD16 +以及TCR-γ/δ + T淋巴细胞表达该抗原。对TCR-α/β + T细胞克隆的分析表明,一小部分(20个中的2个)与CD8和CD56分子一起弱表达Kp43。通过对不同组织进行免疫过氧化物酶染色,抗Kp43反应仅在淋巴器官中检测到,其中少数散在细胞被染色,以及在一些肝窦状细胞中。基本上所有NK细胞在用B淋巴母细胞系刺激后都会获得Kp43。相比之下,T-γ/δ淋巴细胞体外培养时Kp43的分布模式保持稳定,因此根据其表达情况划分出两个亚群。在通过用高浓度白细胞介素-2(IL-2)培养PBL或NK细胞获得的淋巴因子激活的杀伤细胞群体中,大多数CD16 +和CD56 +细胞变为Kp43 +。Kp43特异性单克隆抗体抑制培养的NK细胞和TCR-γ/δ + T细胞的IL-2依赖性增殖反应,而不影响它们的非主要组织相容性复合体(MHC)限制的细胞毒性。胃蛋白酶消化的F(ab')2片段也介导了部分抑制作用,但还原为Fab后这种作用消失。抗Kp43单克隆抗体不干扰IL-2与其表面受体的特异性结合。总之,数据表明Kp43二聚体参与调节NK细胞和一部分TCR-γ/δ + T淋巴细胞的IL-2依赖性增殖反应。

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