IMMUNE RESPONSE GENE REGULATION OF THE IMMUNE RESPONSE IN VITRO

体外免疫反应的免疫反应基因调控

• 批准号: 3813459
• 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/3813459
• 关键词: T lymphocyte; clone cells; genetic regulation; immune response genes; immunogenetics; immunoregulation; laboratory mouse; molecular cloning; mutant; protein sequence; synthetic peptide

In order to 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 clones were restricted to recognizing NASE in the context of either A(alpha)A(beta) or E(alpha)E(beta) products. The antigen fine specificity of cloned NASE-specific T cells was also probed through the use of mutant NASE molecules and synthetic peptides corresponding to segments of NASE. A consistent correlation was found between the fine specificity of a given clone and its MHC restriction specificity. A(b)(alpha)A(b)(beta) restricted clones were selectively responsive to peptide 91-110; E(k)(alpha)E(k)(beta) restricted clones were responsive to peptide 81-100. The nature of the immunogenic peptides which are processed and presented to T cells was further evaluated using a panel of variant NASE peptides. It was observed that negative (inhibitory) interactions appear to occur between amino acids in peptides which interfere with T cell responses. Single amino acid changes, by eliminating such apparent negative interactions result in the restoration of T cell stimulatory ability in these peptides.

为了分析 T 细胞对 NASE 反应的遗传调控， BALB/c (H-2d) 以及 (H-2b x H-2a)F1 T 细胞。单个克隆仅限于识别 NASE A(alpha)A(beta) 或 E(alpha)E(beta) 产品的上下文。这 还探讨了克隆的 NASE 特异性 T 细胞的抗原精细特异性 通过使用突变 NASE 分子和合成肽 对应于 NASE 的片段。发现一致的相关性 给定克隆的精细特异性与其 MHC 限制之间的关系 特异性。 A(b)(alpha)A(b)(beta)限制性克隆被选择性地 对肽 91-110 有反应； E(k)(alpha)E(k)(beta)限制性克隆 对肽81-100有反应。 被加工和呈递给的免疫原性肽的性质 使用一组变体 NASE 肽进一步评估 T 细胞。它 观察到似乎发生了负面（抑制）相互作用 干扰 T 细胞反应的肽中的氨基酸之间。 通过消除这种明显的负面影响，单个氨基酸发生变化 相互作用导致 T 细胞刺激能力的恢复 这些肽。