SUPERANTIGEN CLASS II MHC COMPLEX STRUCTURE AND FUNCTION

超抗原 II 类 MHC 复合体的结构和功能

• 批准号: 6108386
• 负责人: DON C WILEY
• 金额: $ 22.15万
• 依托单位: IMMUNE DISEASE INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-04-01 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6108386
• 关键词: Escherichia coli; MHC class II antigen; T cell receptor; T lymphocyte; X ray crystallography; antigen presentation; bacterial toxins; flow cytometry; laboratory mouse; leukocyte activation /transformation; molecular cloning; polymerase chain reaction; protein structure function; receptor binding; superantigens; tissue /cell culture; toxic shock syndrome

The molecular mechanism by which the superantigen that causes Toxic Shock Syndrome, TSST-l, binds to human class II histocompatibility antigen and T-cell receptors will be studied by high resolution X-ray crystallography. A complex between a soluble form of the class II MHC molecule HLA-DR1 will be crystallized in complex with TSST-l and selected subfragments. A soluble form of alpha-beta T-cell receptor (TCR) that interacts with TSST- l will be constructed and attempts made to form and to crystallize the ternary complex DR1:TSST-1:TCR. A strategy is also proposed for discovering and constructing a soluble form of a gamma-delta TCR that interacts with TSST-1. If successful, this might allow the structure determination of a gamma-delta TCR in an active complex (DR1:TSST-1: gamma-delta TCR).

超抗原引起中毒性休克的分子机制 综合征，TSST-1，与人类 II 类组织相容性抗原结合并 T 细胞受体将通过高分辨率 X 射线晶体学进行研究。 II 类 MHC 分子 HLA-DR1 的可溶形式之间的复合物将 与 TSST-1 和选定的亚片段形成复合物结晶。 一个 可溶形式的 α-β T 细胞受体 (TCR)，与 TSST 相互作用 l 将被构建并尝试形成和结晶 三元复合物 DR1:TSST-1:TCR。 还提出了发现和构建可溶性的策略 与 TSST-1 相互作用的 gamma-delta TCR 形式。 如果成功的话，这 可能允许在活性物质中确定γ-δ TCR的结构 复合物（DR1：TSST-1：gamma-delta TCR）。