T CELL RESPONSE TO AA IN MICE IMMUNIZED SUBCUTANEOUSLY OR ORALLY INFECTED

皮下或口腔感染免疫小鼠中 T 细胞对 AA 的反应

• 批准号: 3732387
• 负责人: PAUL J EZZO
• 金额: --
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 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/3732387
• 关键词: Actinobacillus actinomycetemcomitans; T cell receptor; T lymphocyte; epitope mapping; hybridomas; immunization; infection; laboratory mouse; leukocyte activation /transformation; microorganism immunology; oral bacteria; periodontitis; superantigens

Characterize the T cell response to Aa in mice that have been either immunized subcutaneously or orally infected. Aa has been strongly associated with localized juvenile periodontitis and is one of many species of bacteria found in the gingival pocket of patients with adult periodontitis. It has been shown that both cell mediated and humoral immune responses are important in periodontal diseases. There is also a suspicion that an exaggerated immune response could be responsible for much of the destruction seen, i.e., bone loss, soft tissue destruction. What has not been shown is exactly what interaction at the molecular level is seen between T cells and Aa. We propose to utilize hybridoma technology to ask what are the predominant T cell antigenic epitopes on Aa and to determine whether there is a restricted TcR response in mice. Since an oral infection such as periodontal disease allows for the pathogenic bacteria to adhere and colonize the gingival pocket without direct exposure to the host's immune system, we will ask whether the repertoire differs when mice are infected versus immunized. To characterize the immune response to Aa, we will analyze TcR sequences. If several of the hybridomas we raise have T cell receptors with the same V beta but different junctions, the possibility of a superantigenic response exists. Another possibility is that an immunodominant epitope could exhibit conservation in the junction plus the V regions suggesting a predominant antigenic epitope. By correlating the antigenic specificity with the TcR junctional sequences, we can elucidate the regulation of T cell induction in response to Aa infection. These characteristics of the immune response to Aa are all important considerations in vaccine design.

表征已经接受以下任一种治疗的小鼠中对Aa的T细胞应答： 皮下免疫或口服感染。 Aa与局限性青少年牙周炎密切相关， 在患者牙龈袋中发现的多种细菌之一 成人牙周炎 已经表明，细胞介导和 体液免疫应答在牙周病中是重要的。 有 也有人怀疑，过度的免疫反应可能是导致 对于所看到的大部分破坏，即，骨质流失软组织破坏 但还没有显示的是在分子水平上 在T细胞和Aa之间可见。我们建议利用杂交瘤技术 问Aa上的主要T细胞抗原表位是什么， 确定小鼠中是否存在限制性TcR反应。 由于口腔感染，如牙周病， 病原菌粘附并定植在牙龈袋中， 直接暴露于宿主的免疫系统，我们会问， 当小鼠被感染与被免疫时，库不同。 表征 我们将分析TcR序列。 如果几个 我们培养的杂交瘤细胞具有相同的V β受体， 在连接处，存在超抗原反应的可能性。 另一 免疫显性表位可能表现出保守性， 连接区加上V区表明主要的抗原表位。 通过将抗原特异性与TcR连接序列相关联， 我们可以阐明Aa对T细胞诱导的调节作用， 感染 Aa免疫反应的这些特征都是 疫苗设计中的重要考虑因素。