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

描述：(改编自申请)：建议进行的研究 这个项目是基于正在进行的分子和细胞研究。 流感病毒宿主防御反应的基础。这些 调查人员已经制造出一大批杂交瘤。 产生针对血凝素(GA)或 PrS流感病毒，并有表达Valpha和 识别免疫显性T细胞杂交瘤的Vbeta基因 与HA的110-120位氨基酸残基对应的HA多肽 与氨基酸残基110-120相关的CD4T细胞识别 与I-ED分子相关的由CD4T细胞识别的HA。这个 该项目的具体目标是：(1)研究衰老对健康的影响 流感病毒保护性抗体的体细胞突变。这个 研究人员将产生一大批HA特异性杂交瘤 不同年龄K-基因敲除小鼠的比较 基因的体细胞突变。自发突变的速度将会 在R·波拉克博士提供的转基因品系中进行研究。(2)至 判断衰老是否影响T的持续性和功能 针对流感病毒HA免疫优势表位的细胞克隆。 为了针对流感的免疫优势表位实现这一点 病毒HA。为了实现这一目标，他们将利用转基因技术 从T细胞杂交瘤中表达Va和Vb转基因的小鼠 识别与I-ED-分子相关的HA110-120肽。在……里面 转Valpha和Vbeta基因的转基因小鼠在CD4中表达 和CD8T细胞。CD4T细胞形成增殖性T细胞的能力 不同载体体外孵育后的反应 HA110-120多肽与CD8 T细胞杀伤靶细胞的能力 包被的HA 110-120多肽将被测定。自从人类进化以来 T细胞克隆在老化过程中可能会受到微生物暴露的影响 建议研究衰老期间是否接触流感病毒 影响表达CRT转基因的T细胞克隆。

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.