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：（根据申请人的摘要进行了改编） 本应用程序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结合受体抑制 （Allo抑制）或激活（异源激活）自然杀戮。 t 识别这些受体，研究人员已经定位了基因 控制NK单元附近或LY-49基因座 大鼠染色体4上的凝集素样受体。它们已经表明NK细胞 在同种活化中有缺陷的大鼠也缺乏 LY-49表达。他们已经克隆并测序了5名大鼠的成员 LY-49家族，并提高了对2种LY-49蛋白质反应的mAb。 他们还对与NK细胞有关的受体产生了新的mAb 同种酶，它们克隆了这些受体cDNA。一个受体 （STOK1/2）是一种新型的L-49分子，其他分子包括先前 他们称为NK凝集素的家族，他们称为Stok9。 目的是表明LY-49和Stok9受体控制NK细胞 大鼠的同种抑制作用和同倍激活。为此，他们有 5个具体目标。 1]扩展LY-49抗体的面板 LY-49功能研究。 2]使用阻止或刺激反ly-49 mabs，他们将检查每个LY-49在大鼠NK上的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家族的新成员的cdnas。 4]他们会生产 对新克隆的Stok9蛋白的MABS。 5]就像AIM 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