基于疾病易感性的SSA抗原肽诱导原发干燥综合征模型的建立及模型机制的研究

原发型干燥综合征（Primary Sjögren's syndrome,pSS)是一种主要累及外分泌腺的自身免疫病,但发病机制不明。本课题组首次发现HLA-DRB1*0803与pSS和SSA阳性的pSS高度相关。在前期研究中，我们发现预测了SSA蛋白的HLA-DRB1*0803限制性T细胞表位，并用此SSA表位诱导产生小鼠pSS模型，产生了人pSS相似症状。我们假设，在全面模拟疾病易感性的基础上，可以建立有效和实用的pSS动物模型。为证实这一假设，本课题在选择易感的SSA的T细胞表位（模拟发病机制）的基础上，将筛选易感的小鼠品系（模拟遗传因素）和不同的佐剂（模拟感染等环境因素），尝试建立新型的pSS小鼠模型。在此基础上，深入研究pSS模型发病的免疫学机制，并以临床治疗方案探讨和验证该模型的应用价值,综合这些成果，以期促进人类pSS基础和临床研究。

Primary Sjögren's syndrome (pSS) is one of the most frequent autoimmune systemic diseases, mainly characterized by ocular and oral dryness due to immune injury to the salivary and lacrimal glands. Our group was first discovered HLA-DRB1*0803 is highly correlated with pSS and SSA-positive pSS. In the previous study, we predicted the HLA-DRB1*0803-restricted T cell epitopes in SSA, and induced pSS mouse model by this epitope, which can phenocopy human pSS symptoms. We hypothesize that a effective and practical animal model of pSS can be established based on a comprehensive simulation of disease susceptibility. To confirm this hypothesis, we took the the advantage of the susceptible T-cell epitopes of SSA (mimic pathogenesis), together with the screening of susceptible mouse strains (mimic genetic factors) and different adjuvant (mimic infection environmental factors), try to establish a new mouse model of pSS. Then we will study of the immunological pathogenesis mechanisms of pSS model. And explore and validate the value of the model by clinical treatment medicine. The combination of these results, basic and clinical research would promote human pSS research.