ONTOGENETIC STUDIES OF A NOVEL PAIR OF IG-LIKE RECEPTORS

一对新型 IG 样受体的个体遗传学研究

• 批准号: 2889489
• 负责人: PETER Daniel BURROWS
• 金额: $ 18.04万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-30 至 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2889489
• 关键词: biochemical evolution; cell type; clinical research; developmental immunology; gene expression; human subject; immunoglobulin genes; laboratory mouse; molecular cloning; monoclonal antibody; nucleic acid sequence; polymerase chain reaction; protein isoforms; protein structure function; recombinant proteins

DESCRIPTION (Adapted from Applicant's Description): The goal of these studies is to define human homologues of two new members of the immunoglobulin gene superfamily that the investigators have recently identified in mice and to examine their expression during human development. Coordinately expressed by B-lymphocytes, monocytes/macrophages, granulocytes, and mast cells, the mouse genes are named PIR for paired immunoglobulin-like receptor genes. The two PIR protein isoforms, PIR-A and PIR-B, have very similar extracellular domains but quite different transmembrane and cytoplasmic regions. The distinguishing features of PIR-A and PIR-B suggest that they are activating and inhibitory (braking) receptors, respectively. PIR-B is invariant and encoded by a single copy gene, while the PIR-A proteins exhibit remarkable variability in their extracellular domains. Seven randomly selected PIR-A cDNAs were non-identical and there are multiple PIR-A genes in the mouse genome. The PIR gene family is highly conserved, having been found in mammals, birds, and reptiles. The characteristics of PIR-A and PIR-B and their coordinate expressions in a restricted subset of host defense cells lead to the hypothesis that they play an important regulatory role in humoral, inflammatory and allergic reactions. The known features of PIR-A and PIR-B raise the possibility that they provide recognition elements that could be of special importance in host defense of the fetus and neonate before the adult-type cognate immune system is fully developed. The investigators propose to: 1) Clone and sequence the human homologues to murine PIR-A and PIR-B to determine the extent of the PIR diversity. 2) Produce the corresponding recombinant proteins and use these proteins to produce discriminating monoclonal antibodies and antisera. 3) Define the biochemical features of the human PIR-A and PIR-B homologues and identify associated molecules. 4) Employ the antibody and DNA probes to examine the ontogeny and cellular distribution pattern of the human PIR-A and PIR-B homologues. These studies will permit identification of normal developmental or acquired defects in the expression of this complex gene family and provide a base of information that will lead to clarification of the role of PIR in host defense during the perinatal and adult periods.

描述（改编自申请人的描述）：这些目标 研究的目的是确定两个新成员的人类同源物， 免疫球蛋白基因超家族，研究人员最近 在小鼠中鉴定，并检查它们在人类发育过程中的表达。 由B淋巴细胞、单核细胞/巨噬细胞协调表达， 粒细胞和肥大细胞，小鼠基因被命名为PIR， 免疫球蛋白样受体基因。 两种PIR蛋白同种型PIR-A和PIR-B是一种蛋白质。 PIR-B，具有非常相似的胞外结构域， 跨膜区和胞质区。 PIR-A的特点 和PIR-B表明，它们是激活和抑制（制动） 受体，分别。 PIR-B是不变的，由单个拷贝编码 基因，而PIR-A蛋白在它们的表达中表现出显著的变异性。 胞外结构域。 7个随机选择的PIR-A cDNA， 不相同，小鼠基因组中存在多个PIR-A基因。 的 PIR基因家族是一个高度保守的基因家族，在哺乳动物、鸟类、 和爬行动物 PIR-A和PIR-B的特性及其坐标 在宿主防御细胞的有限子集中的表达导致 假设它们在体液， 炎症和过敏反应。 PIR-A和PIR-B的已知特征 提高了它们提供承认要素的可能性， 在胎儿和新生儿的宿主防御中特别重要， 成人型同源免疫系统发育完全。 调查人员 建议：1）克隆和测序鼠PIR-A的人同源物， PIR-B用于确定PIR多样性的程度。 2)产生 相应的重组蛋白，并使用这些蛋白来生产 区分单克隆抗体和抗血清。 3)定义 人PIR-A和PIR-B同源物的生物化学特征和鉴定 相关分子 4)用抗体和DNA探针检测 人PIR-A和PIR-B的个体发育和细胞分布模式 同源物 这些研究将允许识别正常的 这种复杂基因表达的发育或获得性缺陷 家庭，并提供一个基础的信息，将导致澄清 PIR在围产期和成虫期宿主防御中的作用。