不同佐剂的疫苗可产生截然不同的保护效果，机体免疫应答强度和类型的差异为其主要原因。课题组前期实验发现：佐剂可改变疫苗接种后表位特异性优势应答谱，且与免疫保护差异密切相关。然而，不同佐剂调控表位优势应答的机制尚不清楚。进一步实验发现：APCs抗原递呈过程中关键分子H2-DM表达受不同佐剂影响，并干扰特异性细胞活化，提示佐剂可能通过H2-DM调控表位特异性优势应答。此外，CIITA作为H2-DM的转录激活因子，亦受到上游信号分子MAPK调控。因此，提出科学假设：佐剂可能通过MAPK/CIITA信号通路，调控APCs内H2-DM分子表达，促进显性表位差异化递呈，形成独特的优势应答谱，导致疫苗不同保护效果。本项目拟针对三种常用佐剂CpG、MDP及MPLA，采用动物模型、流式、基因沉默等方法，以揭示佐剂调控优势表位差异化应答的分子机制，为不同佐剂疫苗保护效果差异和疫苗研发提供新的科学解释和理论依据。

Vaccines combined with different adjuvants have different protective effects, which results from the strengths and types of immune responses post the vaccination. In previous research, we found adjuvants affected the T cell response repertoire to antigen epitopes, leading to differences in protective effects. However, the mechanisms of adjuvants regulating epitope-specific response repertoire are not clear. We found that adjuvants regulated the expression of H2-DM, the key molecule during epitope presentation of APCs, suggesting that H2-DM molecule may play a role during the epitope-specific response regulation of adjuvants. It has been confirmed that CIITA, the major H2-DM transcriptional activator, is regulated by MAPK. Thus, we hypothesize that adjuvants regulate the expression of H2-DM molecule through the MAPK / CIITA pathway, which affects epitopes presentation of APCs and causes different protective effects post vaccination. In this project, the methods of flow cytometry, gene silencing and animal models will be used to clarify the mechanisms of adjuvants, CpG, MDP, and MPLA, mediating the different repertoires of epitope-presentation. The data obtained in this study contribute to characterization of the protective effects of vaccines combined with different adjuvants, and can be used to develop new vaccines.