MOLECULAR SITES REACTIVE WITH A SUPERANTIGEN (MAM)

与超抗原 (MAM) 发生反应的分子位点

• 批准号: 3146176
• 负责人: DAVID N POSNETT
• 金额: $ 17.89万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-03-01 至 1996-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3146176
• 关键词: MHC class I antigen; MHC class II antigen; Mycoplasma; T cell receptor; T lymphocyte; bacterial antigens; chimeric proteins; genetic manipulation; leukocyte activation /transformation; molecular cloning; monoclonal antibody; polymerase chain reaction; site directed mutagenesis

DESCRIPTION (Adapted from applicant's abstract): Mycoplasma arthritides superantigen (MAM) is one of several secreted microbial toxins termed superantigens in reference to their potent activation of subsets that share expression of certain TCR V gene products. Dr. Posnett chose to work with MAM because it derives from a microbe that causes an autoimmune-like arthritis in rodents and that can also infect humans. In preliminary studies, a monoclonal antibody (MAb) specific for a TCR V gene product identified a T cell population that was expanded in cultures exposed to MAM. L cells transfected with human DR, but not those transfected with human DQ MHC molecules were able to present MAM to T cell. The current application pursues these results in order to complete the information on MAM-reactive TCR and MHC molecules in human system. The four specific aims are 1) to define all MAM-reactive TCR V gene products, 2) to produce MAb specific for these V gene products, 3) to define MHC isotopes and alleles that may present MAM to MAM-reactive T cells and to determine the contact site(s) for MAM on MHC, and 4) to define the TCR site(s) reactive with the MAM-MHC complex. The latter two aims will require the production of hybrid TCR and MHC molecules by PCR using overlap extension and also site-directed mutagenesis studies. While the functional significance of superantigens is not yet clear, he and others have postulated roles for superagtigens in autoimmunity. It might therefore be useful to understand the exact specificity of a potentially pathogenic superantigen, since vaccines based on the TCR sequences involved could be produced in the future.

描述（改编自申请人的摘要）：支原体关节炎 超抗原（MAM）是所谓的几种分泌微生物毒素之一 超抗原参考其有效激活共享的子集 某些TCR V基因产物的表达。 Posnett博士选择与 MAM是因为它来自导致自身免疫样的微生物 啮齿动物的关节炎，也可以感染人类。 在初步 研究，一种针对TCR V基因产物的单克隆抗体（MAB） 确定了在暴露于培养物中扩展的T细胞群 妈妈。 l被人类DR转染的细胞，但不转染的细胞 人DQ MHC分子能够将MAM呈现给T细胞。 电流 申请追求这些结果，以完成有关 人类系统中的MAM反应性TCR和MHC分子。 四个特定目标 是1）定义所有MAM反应性TCR V基因产物，2）产生mAb 特定于这些V基因产物，3）定义MHC同位素和等位基因 这可能会呈现MAM与MAM反应性T细胞，并确定接触 MAM上的MAM位点，4）定义TCR位点反应性 MAM-MHC复合物。 后两个目标将需要产生混合动力 PCR使用重叠延伸和位置定向的TCR和MHC分子 诱变研究。 虽然超抗原的功能意义尚不清楚，但他和 其他人则假定了超级免疫中超级诱导的角色。 可能 因此，对于了解潜在的确切特异性很有用 致病超抗原，因为基于涉及的TCR序列的疫苗 将来可能会生产。