基于核心序列区构建泛宿主性Th表位预测及优化工具的研究

基于T细胞表位的疫苗在病毒感染、自身免疫性疾病以及肿瘤的治疗中具有广阔的应用前景。由于人白细胞抗原（HLA）具有高度多态性及基因共显性的特点，泛宿主性T细胞表位因其可以被多种HLA分子提呈而成为疫苗设计的首选对象。本研究结合泛宿主性Th表位预测过程中所涉及的主要问题和表位疫苗设计中的关键技术需求，提出一种全新的泛宿主性Th表位预测策略——基于泛宿主性Th表位核心序列区构建预测模型，同时整合具有高区分能力的单HLA-II类分子限制性结合肽的预测方法以及抗原提呈中主要组织相容性复合物（MHC）II类分子特异性的剪切基序，建立基于互联网的泛宿主性Th表位预测和优化工具，实现单HLA-II类分子限制性和泛宿主性Th表位的从头预测以及给定Th表位的优化设计。同时以HBV相关抗原为研究对象，结合免疫学试验验证此工具预测和优化泛宿主性Th表位的性能。

The T cell epitopes have great potential for the development of epitope-based vaccines against viral infections, autoimmune diseases and certain tumors. Because of the high polymorphisms and co-dominance of Human leukocyte antigen (HLA) alleles, promiscuous T cell epitopes that can be presented by multiple HLA molecules are the preferred targets in the development of epitope-based vaccines. Considering the principal problems in the prediction of promiscuous Th epitopes and the key technology in design of the epitope-based vaccines, in this study, we propose a novel method for the prediction of promiscuous Th epitopes — core-sequence-region based method. Furthermore, we will integrate the prediction tool with high discrimination ability for HLA class II allele-specific binding peptides and the MHC class II specific cleavage motifs of antigens in the antigen presentation process into this novel method, and develop a web based tool for prediction and optimization of promiscuous Th epitopes, which can be able to predict and optimize the HLA-II allele-specific and promiscuous Th epitopes. The efficiency of this web-based tool in predicting and optimizing promiscuous Th epitopes will be validated by peptide immunization experiments using the corresponding epitopes from HBV related antigens.