ONTOGENETIC STUDIES OF A NOVEL PAIR OF IG-LIKE RECEPTORS

描述(改编自申请者的描述)：这些目标 研究是为了定义人类同源基因的两个新成员 研究人员最近发现的免疫球蛋白基因超家族 并检测它们在人类发育过程中的表达。 由B淋巴细胞、单核/巨噬细胞、 小鼠的粒细胞和肥大细胞的基因被命名为PIR 免疫球蛋白样受体基因。两种PIR蛋白亚型，PIR-A和PIR-A PIR-B具有非常相似的胞外结构域，但却有很大的不同 跨膜区和胞浆区。PIR-A的特点 和PIR-B表明它们正在激活和抑制(刹车) 分别是受体。PIR-B是不变的，并由单个副本编码 基因，而PIR-A蛋白表现出显著的变异性 胞外结构域。随机选择的7个PIR-A cDNA 小鼠基因组中存在多个PIR-A基因。这个 PIR基因家族高度保守，已在哺乳动物、鸟类、 还有爬行动物。PIR-A和PIR-B的特性及其配位 在有限的宿主防御细胞子集中的表达会导致 假设它们在体液中起着重要的调节作用， 炎症和过敏反应。PIR-A和PIR-B的已知特征 提高了它们提供的识别元素可能是 在宿主保护胎儿和新生儿方面具有特别重要的意义 成人型同源免疫系统发育充分。调查人员 建议：1)克隆和测序小鼠PIR-A和PIR-A的人类同源物 PIR-B来确定PIR分集的程度。2)制作 相应的重组蛋白，并用这些蛋白产生 鉴别单抗和抗血清。3)定义 人PIR-A和PIR-B同源物的生化特征及鉴定 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 同源同源。这些研究将允许识别正常 这种复杂基因表达的发育或获得性缺陷 并提供信息基础，将导致澄清 PIR在围产期和成年期宿主防御中的作用。

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.