IMMUNE RESPONSE GENE REGULATION OF IMMUNE RESPONSE IN VITRO

体外免疫反应的免疫反应基因调控

• 批准号: 4691763
• 负责人: R J HODES
• 金额: --
• 依托单位: DIVISION OF CANCER BIOLOGY AND DIAGNOSIS
• 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/4691763
• 关键词: B lymphocyte; T lymphocyte; antibody formation; cellular immunity; clone cells; gene complementation; gene expression; genetic mapping; genetic regulation; genetic strain; histocompatibility antigens; immune response genes; leukocyte activation /transformation; linkage mapping; major histocompatibility complex; monoclonal antibody; mutant; nitrophenol; nuclease; spleen; stainings; synthetic peptide; tissue /cell culture; tissue mosaicism

The cellular expression of immune response (Ir) gene function was studied in both primary and secondary in vitro antibody responses to the TNP conjugates of (T,G)-A--L and (H,G)-A--L. The function of accessory cells in responses to TNP-(T,G)-A--L and TNP-(H,G)-A--L is under the control of genes which also map to I-A. In contrast, the expression of Ir gene function by B cells is related to the B cell activation pathway; Ir gene function is expressed by B cells activated under conditions involving MHC-restricted T-B interaction. In vitro augmented primary and secondary responses to TNP-nuclease (TNP-NASE) have also been established and documented to be under the control of H-2 linked Ir gene(s) mapping to the I-B subregion. For these responses, accessory cell function was shown to be under Ir gene control. Recent data employing monoclonal anti-Ia reagents have suggested that genes in the I-A subregion may also be involved in regulating responses to TNP-NASE. In order to further analyze the genetic regulation of T cell responses to NASE, a series of cloned lines were generated in BALB/c (H-2d) as well as (H-2b x H-2a)F1 T cells. Individual BALB/c clones were restricted to recognizing NASE in the context of either I-Ad or I-E products. Individual F1 clones were specific for NASE in association with either H-2a or H-2b antigen-presenting cells and subregion mapping studies are currently in progress. The antigen fine specificity of cloned NASE-specific T cells is also being probed through the use of mutant NASE molecules, synthetic peptides corresponding to segments of NASE, and monoclonal antibodies specific for different determinants on the NASE molecule.

研究免疫应答（Ir）基因功能的细胞表达 在对TNP的一级和二级体外抗体应答中 （T，G）-A-L和（H，G）-A-L的缀合物。 辅助细胞的功能 在对TNP-（T，G）-A-L和TNP-（H，G）-A-L的响应中， 也映射到I-A的基因。 相反，Ir基因的表达 B细胞的功能与B细胞活化途径有关; Ir基因 功能由B细胞表达，所述B细胞在包括以下的条件下活化： MHC限制性T-B相互作用。 体外增强的初级和次级 对TNP-核酸酶（TNP-NASE）的反应也已经建立， 记录为在H-2连锁Ir基因的控制下， I-B次区域。 对于这些反应，辅助细胞功能被证明是 受Ir基因控制。 使用单克隆抗Ia抗体的最新数据 试剂表明，I-A亚区的基因也可能是 参与调节对TNP-NASE的反应。 为了进一步分析 T细胞对NASE反应的遗传调节，一系列克隆的 在BALB/c（H-2d）以及（H-2b x H-2a）F1 T细胞中产生细胞系。 单个BALB/c克隆仅限于识别背景中的NASE。 I-Ad或I-E产品的销售。 单个F1克隆特异于 与H-2a或H-2b抗原呈递细胞相关的NASE， 目前正在进行次区域绘图研究。 克隆的NSE特异性T细胞的抗原精细特异性也正在研究中。 通过使用突变的NASE分子，合成肽， 对应于NASE片段的单克隆抗体，和特异于 不同的决定因素。