STUDIES OF THE STRUCTURES OF FCY RECEPTORS

这项赠款提案的目的是：(1)进一步描述 人单核细胞中结构独特的FcGamma受体B 淋巴细胞和非B淋巴细胞。纯化的细胞群体将是 用放射性同型标记，放射性标记的FcGamma受体将 通过重复层析进行分离。标记的FcGamma受体将 用十二烷基硫酸钠-聚丙烯酰胺凝胶电泳法分析。胰蛋白酶多肽 独特受体及其片段的图谱和氨基酸序列 将进行同源性检查。(2)FcGamma的分离和鉴定 其他人类白细胞的受体，如嗜酸性粒细胞、人类细胞 株系，白血病细胞使用类似的程序。(3)制备单抗 针对每个不同的人类FcGamma受体的抗体。F(Ab)和 F(Ab)‘S的单抗蛋白片段将被仔细鉴定以 严格记录抗受体活性。(4)研究互动 在不同的人类FcGamma受体和免疫球蛋白之间 不同于亚纲、阶级、起源物种或聚集状态。(5) 以确定人类FcGamma受体是否具有多种成分。 生物合成放射性标记受体和化学交联 将检查受体，以寻找可能的证据和特性 相关分子。(6)如果FcGamma受体是磷蛋白，则 检查受体是否选择性磷酸化(或 去磷酸化)在非特异性或免疫细胞激活过程中。 (涉及的学科有免疫学、蛋白质化学和细胞 生物学。)这些目标将推动我们的长期目标：(A)学习 关于结构上的分布、结构和功能 独特的人类FcGamma受体，它们与免疫球蛋白的相互作用， 以及它们的作用机制。(B)确定FcGamma受体是否 可能涉及白血病的并发症以及是否检测到 独特的FcGamma受体可能在淋巴瘤分类和 治疗。(C)了解免疫缺陷的机制和其他 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.