ANTIGEN RECOGNITION AND ACTIVATION OF IMMUNOCOMPETENT CELLS

免疫活性细胞的抗原识别和激活

• 批准号: 3746448
• 负责人: W E PAUL
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3746448
• 关键词: B lymphocyte; T lymphocyte; antibody formation; antibody receptor; antigen antibody reaction; antigens; basophils; cell growth regulation; electrophoresis; gene frequency; gene rearrangement; genetic mapping; genetic regulation; hybridomas; immune tolerance /unresponsiveness; immunogenetics; immunoglobulin G; immunoglobulin genes; immunoglobulins; immunoregulation; inborn immunodeficiency; interleukin 2; interleukin 4; interleukin 5; laboratory mouse; leukocyte activation /transformation; major histocompatibility complex; mast cell; monoclonal antibody; neoplastic cell; point mutation; polymerase chain reaction; protein tyrosine kinase; sex linked trait

A specific and quantitative assay for measuring the frequency of chromosomes in which Ig class switch events have occurred has been developed. This quantitative and specific assay, digestion- circularization PCR (DC-PCR), allows one to measure the frequency of chromosomes on which deletional switching has occurred. A critical role for the cytokine interleukin-5 (IL-5) in the initiation of the class switch event has been demonstrated in B cells stimulated with anti- immunoglobulin antibodies and interleukin-4 (IL-4). Although IL-4 targets certain switch regions for recombination, virtually no recombination events occur unless IL-5 is also present. Efforts to analyze the molecules induced by IL-5 that control recombination are now in progress. The X-linked immunodeficiency of CBA/N mice has been shown to be caused by a point mutation in the gene for the tyrosine kinase btk that converts amino acid 28, within the plekstrin homology domain of the kinase, from arginine to cysteine. Basophils and mast cells secrete IL-4 and other cytokines as a result of cross-linkage of Fc receptors and elevation of intracellular calcium. Human basophils secrete IL-4 in response to cross-linkage of FcgammaRII. However, this receptor transduces distinct signals depending upon the ligand. Thus, immobilized IgG4 induces IL-4 production while immobilized IgG1 does not although it does bind to the receptor and, under very specific conditions, enhances IL-4 production in response to immobilized IgG4. This indicates that IgG1 may act as an antagonist or a partial agonist depending upon conditions, which may have important physiologic significance.

用于测量频率的特定和定量测定 发生IG类转换事件的染色体已有 发达。 这种定量和特定的分析，消化 - 循环PCR（DC-PCR）允许一个人测量 发生缺失开关的染色体。 关键作用 对于班级开始的细胞因子白介素5（IL-5） 在用抗刺激的B细胞中证明了开关事件 免疫球蛋白抗体和白介素-4（IL-4）。 虽然IL-4 针对某些开关区域进行重组，几乎没有 除非存在IL-5，否则会发生重组事件。 努力 分析IL-5诱导的分子现在，控制重组已 进行中。 CBA/N小鼠的X连锁免疫缺陷已被证明是引起的 通过转换酪氨酸激酶BTK的基因中的点突变 氨基酸28，在激酶的Plekstrin同源域内，从 精氨酸到半胱氨酸。 嗜碱性粒细胞和肥大细胞分泌IL-4和其他细胞因子。 FC受体的交叉链接和细胞内钙的升高。 人类嗜碱性粒细胞分泌IL-4，以响应fcgammarii的交联。 但是，该受体会根据 配体。 因此，固定的IgG4诱导IL-4产生，同时固定 IgG1尽管它确实与受体结合，并且在非常 特定条件，增强IL-4的产生，以响应于固定的 IgG4。 这表明IgG1可以充当拮抗剂或部分 激动剂取决于条件，这可能具有重要的生理 意义。