THE EFFECT OF AGE ON MOLECULAR STRUCTURE AND FUNCTION OF THE ANTIGEN RECEPTOR

年龄对抗原受体分子结构和功能的影响

• 批准号: 6098756
• 负责人: CONSTANTIN A BONA
• 金额: $ 21.97万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-01 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6098756
• 关键词: B lymphocyte; MHC class II antigen; Paramyxovirus; T cell receptor; aging; antigen receptors; apoptosis; cellular immunity; clone cells; cytotoxic T lymphocyte; flow cytometry; gene frequency; gene mutation; genetically modified animals; helper T lymphocyte; hemagglutinin; humoral immunity; hybridomas; immunosenescence; interleukin 10; interleukin 4; laboratory mouse; monoclonal antibody; nucleic acid sequence; virus antigen

DESCRIPTION: (adapted from the application): The studies proposed in this project are based on ongoing research on the molecular and cellular basis of host defense reactions against influenza virus. These investigators have already produced a large panel of hybridomas producing monoclonal antibodies specific for the hemagglutinin (GA) or PRS influenza virus and have transgenic mice expressing the Valpha and Vbeta genes of a T cell hybridoma that recognize an immunodominant peptide of HA corresponding to amino acid residues 110-120 of HA recognized by CD4 T cells in association to amino acid residues 110-120 of HA recognized by CD4 T cells in association with I-Ed molecules. The specific aims of the project are: (1) To study the effect of aging on somatic mutation in protective antibodies against influenza virus. The investigators will generate a large panel of HA-specific hybridomas from K-knockout mice of various ages in order to compare the extent of somatic mutations in the genes. The rate of spontaneous mutations will be studied in transgenic line provided by Dr. R. Pollack. (2) To determine whether aging influences the persistence and function of T cell clone specific for an immunodominant epitope of influenza virus HA. To achieve this specific for an immunodominant epitope of influenza virus HA. To achieve this aim they will take advantage of transgenic mice which express Va and Vb transgene from a T cell hybridoma that recognizes HA110-120 peptide in association with I-Ed- molecules. In the transgenic mice the Valpha and Vbeta transgenes are expressed in CD4 and CD8 T cells. The ability of CD4 T cells to develop a proliferative response upon in vitro incubation with various carriers expressing HA110-120 peptide and the ability of CD8 T cells to lyse target cells coated HA 110-120 peptide will be determined. Since the evolution of a T cell clone may be affected by microbial exposure during aging they propose to study whether the exposure to influenza virus during aging affects the T cell clone expressing the CRT transgene.

描述：（改编自申请）： 该项目是基于正在进行的分子和细胞研究， 宿主对流感病毒的防御反应的基础。 这些 研究人员已经制造出一大批杂交瘤细胞， 产生对血凝素（GA）特异的单克隆抗体，或 PRS流感病毒，并具有表达Valpha和 T细胞杂交瘤的Vbeta基因，其识别免疫显性的 HA的肽，对应于HA的氨基酸残基110-120 与氨基酸残基110-120相关的CD 4 T细胞识别 与I-Ed分子相关的由CD 4 T细胞识别的HA。 的 该项目的具体目标是：（1）研究衰老对 流感病毒保护性抗体的体细胞突变。 的 研究人员将从以下来源产生大量HA特异性杂交瘤： 不同年龄的K基因敲除小鼠，以比较 基因中的体细胞突变 自发突变的速率 在R.波拉克 (2)到 确定衰老是否影响T细胞的持久性和功能 对流感病毒HA免疫显性表位特异的细胞克隆。 为了实现对流感的免疫显性表位的特异性， 病毒HA。 为了实现这一目标，他们将利用转基因技术 表达来自T细胞杂交瘤的Va和Vb转基因的小鼠， 识别与I-Ed-分子结合的HA 110 -120肽。 在 在转基因小鼠中，Valpha和Vbeta转基因在CD 4+细胞中表达， CD 8 T细胞 CD 4 T细胞发展增殖性T细胞的能力 在与表达以下的各种载体体外孵育后的应答 HA 110 -120肽和CD 8 T细胞裂解靶细胞的能力 将确定包被的HA 110-120肽。 自进化以来， T细胞克隆可能会受到老化过程中微生物暴露的影响， 建议研究在衰老过程中接触流感病毒是否 影响表达CRT转基因的T细胞克隆。