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: 2736488
• 负责人: JAMES C RYAN
• 金额: $ 26.13万
• 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 2004-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2736488
• 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：(改编自申请者的摘要) 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类分子的识别。功能研究 提示大鼠NK细胞必须表达MHC结合受体抑制物 (同源抑制)或激活(同源激活)自然杀伤。T 识别这些受体，研究人员已经定位了基因 控制Ly-49位点附近或内的NK细胞同种异体反应 大鼠4号染色体上的凝集素样受体。他们已经表明，NK细胞 同种异体激活有缺陷的形式的大鼠也缺乏 LY-49的表达。他们已经克隆了这只大鼠的5个成员并进行了测序 Ly-49家族，并已提高了与2个Ly-49蛋白反应的单抗。 他们还产生了针对NK细胞中涉及的受体的新单抗 异体反应，他们已经克隆了这些受体cDNA。一种受体 (STOK1/2)是一个新的L-49分子，其他分子都包含一个以前的 未被描述的NK凝集素家族，他们称之为STOK9。 目的研究Ly-49和STOK9受体对NK细胞的调控作用 大鼠同种异体抑制和同种异体激活。为了达到这个目的，他们有 5具体目标。1]扩大Ly-49抗体组，用于 LY-49的功能研究。2]使用阻断或刺激抗Ly-49 单抗，他们将检查每种Ly-49对大鼠NK细胞的MHC特异性 细胞和转Ly-49基因的RNK-16细胞。3]他们会克隆人 编码STOK9家族新成员的DNA。4]他们将生产 针对新克隆的STOK9蛋白的单抗。5]与《目标2》中一样，他们将 用这些试剂检测STOK9受体的MHC特异性 大鼠NK细胞和转导STOK9的RNK-16细胞株。