RAE-1 Family of Proteins in Innate and Adaptive Immunity

先天性和适应性免疫中的 RAE-1 蛋白家族

基本信息

批准号：
6839417
负责人：
LEWIS Lee LANIER
金额：
$ 30.34万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-02-14 至 2008-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6839417
关键词：
RAE Family Proteins Innate Adaptive

项目摘要

EXCEED THE SPACE PROVIDED. Natural killer (NK) cells participate in the innate immune response against pathogens and tumors. There is growing evidence that they are involved in allograft rejection and possibly in certain autoimmune diseases. The receptors on NK cells responsible for their activation are only now being appreciated. One of these receptors, NKG2D has been implicated in the ability of NK cells to kill certain tumors and virus-infected cells. NKG2D is present on all NK cells, CDS+T cells, y6-TcR + T cells and some activated macrophages. Recently, we and others cloned a family of mouse genes, designated RAE-1, encoding MHC class I-like proteins that bind with high affinity to mouse NKG2D. Human orthologs of the RAE-1 genes (designated as either ULBP or RAE-l-like genes) have been identified and the proteins encoded by these genes are recognized by the human NKG2D receptor. In humans, the NKG2D receptor also recognizes MICA and MICB, polymorphic MHC class I antigens that are induced by stress, transformation and viral infection. Emerging evidence suggests that the RAE-1 and MIC glycoproteins may serve to trigger the innate immune responses mediated by NK cells and yS-TcR +T cells and function to co-stimulate antigen-specific responses by CD8 + cytotoxic T lymphocytes. We propose to investigate the RAE-I family of genes and determine their role in innate and adaptive immune responses. The specific aims of this program are: 1) to determine whether the RAE-1 genes are polymorphic, analyze their expression and determine if they elicit allogeneic responses, 2) to establish the relevance of induction of the RAE-1 molecules during viral infection, to determine how the human CMV UL 16 protein and potentially other viral proteins interfere with RAE-1, and to evaluate whether viruses other than HCMV induce the RAE-1 genes, and 3) to evaluate the mechanisms responsible for the induction of the RAE-1 genes in normal cells. The overall objective of this project is to understand both the beneficial and potentially adverse functions of the RAE- 1 family of antigens in innate and adaptive immune responses. PERFORMANCE SITE ========================================Section End===========================================

超出所提供的空间。自然杀伤 (NK) 细胞参与针对病原体和肿瘤的先天免疫反应。越来越多的证据表明它们与同种异体移植排斥有关，并可能与某些自身免疫性疾病有关。 NK 细胞上负责其激活的受体现在才被人们所认识。 NKG2D 是这些受体之一，与 NK 细胞杀死某些肿瘤和病毒感染细胞的能力有关。 NKG2D 存在于所有 NK 细胞、CDS+T 细胞、y6-TcR+T 细胞和一些活化的巨噬细胞上。最近，我们和其他人克隆了一个小鼠基因家族，命名为 RAE-1，编码 MHC I 类蛋白，与小鼠 NKG2D 具有高亲和力结合。 RAE-1基因的人类直系同源物（指定为ULBP或RAE-1样基因）已被鉴定，并且由这些基因编码的蛋白质被人类NKG2D受体识别。在人类中，NKG2D 受体还识别 MICA 和 MICB，这是由压力、转化和病毒感染诱导的多态性 MHC I 类抗原。新的证据表明，RAE-1 和 MIC 糖蛋白可能有助于触发 NK 细胞和 yS-TcR + T 细胞介导的先天免疫反应，并共同刺激 CD8 + 细胞毒性 T 淋巴细胞的抗原特异性反应。我们建议研究 RAE-I 基因家族并确定它们在先天性和适应性免疫反应中的作用。该计划的具体目标是：1) 确定 RAE-1 基因是否具有多态性，分析其表达并确定它们是否引发同种异体反应，2) 确定病毒感染期间 RAE-1 分子诱导的相关性，确定人类 CMV UL 16 蛋白和潜在的其他病毒蛋白如何干扰 RAE-1，并评估 HCMV 以外的病毒是否诱导 RAE-1 基因，以及 3) 评估诱导 RAE-1 基因的机制正常细胞中的 RAE-1 基因。该项目的总体目标是了解 RAE-1 抗原家族在先天性和适应性免疫反应中的有益和潜在不利功能。表演网站==========================================部分结束====== =======================================