项目名称: I 型组织相容性复合物(MHC-I) 轻链β2微球蛋白(β2m)在抗细菌感染免疫中的作用及其机制
项目编号: No.31370928
项目类型: 面上项目
立项/批准年度: 2014
项目学科: 免疫学
项目作者: 王北难
作者单位: 中国科学院微生物研究所
项目金额: 80万元
中文摘要: 抗体和T细胞介导的获得性免疫在抗感染免疫中发挥主要作用。MHC-I的轻链β2微球蛋白(β2m)调节抗体水平和CD8 T细胞功能,但β2m在抗感染免疫中的作用和机制缺乏研究。我们发现细菌抗原与β2m同时免疫小鼠后特异性抗体水平显著增高,说明β2m在抗感染免疫中有不可忽视的作用。本项目将从抗体和CD8 T细胞的两个方面研究β2m在抗感染免疫中的作用和机理,设以下两个课题。课题一证实β2m促进抗原特异性抗体增高的机制,通过对免疫后抗体水平和抗体半衰期的分析,确定β2m在抗体产生和代谢中的作用,并用小鼠感染模型证实β2m增强对粘膜细菌感染的保护效应。课题二通过对β2m 在CD8 T细胞的活化、功能和免疫保护效应的分析,确定β2m在CD8 T细胞介导的抗胞内菌感染中的作用。探索β2m在感染免疫保护中的佐剂作用和机制将为疫苗的发展在理论上和应用上开辟新途径。
中文关键词: 佐剂;抗体;CD8;T细胞;粘膜免疫;细菌免疫
英文摘要: Antibody and T cell-mediated adaptive immunity play important roles in protection against microbial infection. It has been known that β2 microglobulin (β2m) regulates antibody levels and CD8 T cell functions; however, the role of β2m in the immunity to microbial infection and the mechanisms underlying anti-microbial responses have not been studied. We found that immunization of mice with bacterial antigen and β2m significantly increased antigen-specific antibodies, indicating that β2m plays an unnegligible role in anti -infection. The project will study the impact of β2m on infection and immunity by following two specific aims: 1) investigate the influence of β2m on antibody levels by asking whether β2m promotes antigen-specific antibody production or reduces antibody metabolism ; and prove β2m enhances protection against bacterial infection with a mouse mucosal infection model. 2) verify the role of β2m in CD8 T cell mediated immunity to intracellular bacterial infection by analysis of CD8 T cell activation and function in the presence and absence of exogenous recombinant β2m. Exploring adjuvant mechanisms of β2m in immune protection will open up important new avenue for vaccine development in both basic research and application.
英文关键词: Adjuvant;Antibody;CD8 T cell;Mucosal immunity;Immunity to bacterial infection