膜性肾病是一种自身免疫性肾小球疾病，其主要的致病抗原是肾小球足细胞上的M型磷脂酶A2受体(PLA2R)。近期的研究已经精确解析了PLA2R抗原的B细胞表位，但其T细胞表位目前仍不清楚。我们的前期研究发现HLA-DRB1*15:01和DRB3*02:02是PLA2R相关膜性肾病的两个独立HLA致病基因型，几乎所有的患者（99%）都携带了至少一个致病HLA基因型，这一发现使得鉴定在致病HLA基因型背景下的PLA2R抗原T细胞表位成为可能。本项目计划在上述两个HLA致病基因型的背景下，鉴定膜性肾病PLA2R抗原的T细胞表位。T细胞表位获得鉴定后，我们将据此建立外周血抗原特异性T细胞的检测新技术，明确此技术在疾病诊断、病情监测及预后判断中的价值，推动其应用于临床实践。更为重要的是，PLA2R抗原T表位的鉴定还将为设计抗原特异性新疗法治疗膜性肾病奠定基础。

Membranous nephropathy (MN) is an organ-specic autoimmune disease and a major cause of adult nephrotic syndrome. The M-type phospholipase A2 receptor (PLA2R) was identified as the major target podocyte antigen. Previous studies identified the immunodominant antigenic epitope in PLA2R responsible for autoantibody binding (B cell epitope), however, its T cell epitopes remain unknown. Recently, we found that the HLA-DRB1*15:01 and HLA-DRB3*02:02 alleles are independently and strongly associated with PLA2R-related MN. Virtually all patients with PLA2R-related MN carry either or both of the HLA-DRB1*15:01 and HLA-DRB3*02:02 alleles. Our findings make it possible to further identify the T cell epitopes of the PLA2R antigen in a specific pathogenic HLA context. The precise T epitope of PLA2R will allow us to detect PLA2R-specific T cells in peripheral blood of patients. Then,we will determine the role of PLA2R-specific T cells in disease diagnosis, disease activity and outcome predicting. More importantly, the identification of T epitopes of PLA2R may also make it possible to design new antigens-specific treatments for PLA2R-related MN in the future.