STUDIES OF THE STRUCTURES OF FCY RECEPTORS

本基金的目的是：（1）进一步描述 从人单核细胞分离的结构独特的Fc γ受体，B 淋巴细胞和非B淋巴细胞。 纯化的细胞群将 用放射性同种型标记，放射性标记的Fc γ受体 通过重复色谱分离。 标记的Fc γ受体将 通过SDS-聚丙烯酰胺凝胶电泳进行分析。 胰蛋白酶肽 独特受体及其片段的图谱和氨基酸序列 将检查同源性。 (2)分离并表征Fc γ 其它人类白细胞群体的受体，例如嗜酸性粒细胞、人类细胞 线，白血病细胞使用类似的程序。 (3)制备单克隆 针对每种不同的人Fc γ受体的抗体F（ab）和 单克隆蛋白的F（ab）片段将被仔细表征， 严格记录抗受体活性。 (4)来研究 在不同的人Fc γ受体和免疫球蛋白之间， 不同的子类，类，物种的起源，或聚集状态。 （五） 确定人Fc γ受体是否具有多种组分。 生物合成放射性标记受体和化学交联 受体将被检查的证据，和属性，可能的， 相关分子 (6)如果Fc γ受体是磷蛋白， 检查受体是否被选择性磷酸化（或 去磷酸化）。 （涉及的学科包括免疫学、蛋白质化学和细胞生物学。 biology.） 这些目标将促进我们的长期目标： 关于结构的分布，结构和功能 独特的人Fc γ受体，它们与免疫球蛋白的相互作用， 及其作用机制。 (b)确定Fc γ受体是否 可能参与白血病的并发症， 独特的Fc γ受体可用于淋巴瘤分类， 治疗 (c)了解免疫缺陷和其他 免疫性疾病。

The aims of this grant proposal are: (1) To further characterize the structurally unique FcGamma receptors isolated from human monocytes, B lymphocytes, and non-B lymphocytes. Purified cell populations will be labeled with radioactive isotypes, and radiolabeled FcGamma receptors will be isolated by repetitive chromatography. Labeled FcGamma receptors will be analyzed by SDS-polyacrylamide gel electrophoresis. Tryptic peptide maps and amino acid sequences of the unique receptors and their fragments will be examined for homology. (2) To isolate and characterize the FcGamma receptors of other human leukocyte populations e.g. eosinophils, human cell lines, leukemia cells using similar procedures. (3) To prepare monoclonal antibodies against each of the distinct human FcGamma receptors.F(ab) and F(ab)'s fragments of monoclonal proteins will be carefully characterized to rigorously document anti-receptor activity. (4) To study interactions between the distinct human FcGamma receptors and immunoglobulins which differ by subclass, class, species of origin, or state of aggregation. (5) To determine whether human FcGamma receptors have multiple components. Biosynthetically radiolabeled receptors and chemically crosslinked receptors will be examined for evidence of, and properties of, possible associated molecules. (6) If FcGamma receptors are phosphoproteins, to examine whether receptors are selectively phosphorylated (or dephosphorylated) during non-specific or immunologic cell activation. (Disciplines involved are immunology, protein chemistry, and cell biology.) These aims will further our long term objectives: (a) Learning about the distributions, structures, and functions of the structurally unique human FcGamma receptors, their interactions with immunoglobulins, and their mechanisms of action. (b) Determining whether FcGamma receptors may be involved in complications of leukemia and whether detection of unique FcGamma receptors may be useful in lymphoma classification and treatment. (c) Understanding mechanisms of immunodeficiency and other immunologic diseases.