CONTROL OF ALLOGENIC NK CELL LYSIS BY LECTIN RECEPTORS

通过凝集素受体控制同种异体 NK 细胞裂解

• 批准号: 6632182
• 负责人: JAMES C RYAN
• 金额: $ 29.41万
• 依托单位: NORTHERN CALIFORNIA INSTITUTE/RES/EDU
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-03-01 至 2005-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6632182
• 关键词: MHC class I antigen; lectin; leukocyte activation /transformation; molecular cloning; monoclonal antibody; natural killer cells; receptor; receptor binding; tissue /cell culture; transfection

DESCRIPTION: (Adapted from the applicant's abstract) The goal of the project described in this application is to define the receptor systems controlling the recognition of MHC I by rat NK cells. Functional studies show that rat NK cells must express MHC-binding receptors inhibits (allo-inhibition) or activates (allo-activation) natural killing. T identify these receptors, the investigators have localized the genes controlling NK cell alloresponses near or within the Ly-49 locus of lectin-like receptors on rat chromosome 4. They have shown that NK cells form rats that are defective in alloactivation are also deficient in Ly-49 expression. They have cloned and sequenced 5 members of the rat Ly-49 family and have raised mAbs reactive against 2 Ly-49 proteins. They have also produced new mAbs against receptors implicated in NK cell alloresponses, and they have cloned these receptor cDNAs. One receptor (STOK1/2) is a novel L-49 molecule, and the others comprise a previously undescribed family of NK lectins, which they have termed STOK9.Their objective is to show that the Ly-49 and STOK9 receptors control NK cell allo-inhibition and allo-activation in rats. Toward this end they have 5 specific aims. 1] Expand the panel of Ly-49 antibodies for use in Ly-49 functional studies. 2] Using blocking or stimulating anti-Ly-49 mAbs, they will examine the MHC specificities of each Ly-49 on rat NK cells and on Ly-49-transfected RNK-16 cell lines. 3] They will clone cDNAs encoding new members of the STOK9 family. 4] They will produce mAbs specific for newly cloned STOK9 proteins. 5] As in Aim 2, they will use these reagents to examine the MHC specificities of STOK9 receptors on rat NK cells and on STOK9-transfected RNK-16 cell lines.

描述：（改编自申请人的摘要）该项目的目标 本申请中描述的项目是定义受体系统 控制大鼠 NK 细胞对 MHC I 的识别。功能研究 表明大鼠 NK 细胞必须表达 MHC 结合受体 （同种异体抑制）或激活（同种异体激活）自然杀伤。时间 识别这些受体后，研究人员已经定位了这些基因 控制 Ly-49 位点附近或内部的 NK 细胞同种异体反应 大鼠 4 号染色体上的凝集素样受体。他们表明 NK 细胞 同种激活有缺陷的大鼠也缺乏 Ly-49 表达。他们克隆并测序了 5 名老鼠成员 Ly-49 家族并已产生针对 2 种 Ly-49 蛋白的单克隆抗体。 他们还生产了针对 NK 细胞相关受体的新单克隆抗体 同种异体反应，他们已经克隆了这些受体 cDNA。一种受体 (STOK1/2) 是一种新型 L-49 分子，其他分子包括先前的 未描述的 NK 凝集素家族，他们将其称为 STOK9。 目的是证明 Ly-49 和 STOK9 受体控制 NK 细胞 大鼠的同种异体抑制和同种异体激活。为此他们有 5个具体目标。 1] 扩展 Ly-49 抗体组，用于 Ly-49 功能研究。 2]使用阻断或刺激抗Ly-49 mAbs，他们将检查每个 Ly-49 对大鼠 NK 的 MHC 特异性 细胞和 Ly-49 转染的 RNK-16 细胞系。 3]他们会克隆 编码 STOK9 家族新成员的 cDNA。 4]他们将生产 针对新克隆的 STOK9 蛋白的单克隆抗体。 5] 正如目标 2 一样，他们将 使用这些试剂检查 STOK9 受体的 MHC 特异性 在大鼠 NK 细胞和 STOK9 转染的 RNK-16 细胞系上。

项目成果

Inhibitory receptors alter natural killer cell interactions with target cells yet allow simultaneous killing of susceptible targets.

抑制性受体改变自然杀伤细胞与靶细胞的相互作用，但允许同时杀死敏感靶标。

• DOI: 10.1084/jem.190.7.1005
• 发表时间: 1999-10-04
• 期刊: JOURNAL OF EXPERIMENTAL MEDICINE
• 影响因子: 15.3
• 作者: Eriksson, M;Leitz, G;Fallman, E;Axner, O;Ryan, J C;Nakamura, M C;Sentman, C L
• 通讯作者: Sentman, C L