Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
J Invest Dermatol. 2018 Sep;138(9):1917-1924. doi: 10.1016/j.jid.2018.03.1515. Epub 2018 Mar 26.
Bullous pemphigoid (BP) is a subepidermal autoimmune blistering disease caused by autoantibodies targeting the juxtamembranous extracellular noncollagenous 16A (NC16A) domain of human collagen XVII (also known as BP180). Because T-helper (Th) cells are essential for antibody responses to antigens, we adopted an assay to map the immunodominant Th2-cell epitopes in NC16A. We synthesized 22 overlapping peptides spanning the entire sequence of BP180-NC16A and investigated the reactivity of Th2 cells from patients with BP to these peptides using the Enzyme-Linked ImmunoSpot (ELISPOT) assay. We screened two epitope peptides, P2 (492-506 aa: VRKLKARVDELERIR) and P5 (501-515 aa: ELERIRRSILPYGDS), and confirmed that these epitopes play a dominant role in stimulating CD4 T-cell proliferation and Th2 IL-4 cytokine production, and activating B cells to secrete autoantibodies. These immunodominant epitopes are HLA-DR-restricted and were observed in subjects with different HLA alleles. This work contributes to elucidation of the epitope-mediated immunologic pathogenesis of BP, and the identified Th2-cell epitopes are candidates for epitope-specific therapeutic strategy.
大疱性类天疱疮（BP）是一种表皮下自身免疫性水疱病，由针对人Ⅶ型胶原第十七链（也称为 BP180）的跨膜区外非胶原 16A（NC16A）结构域的自身抗体引起。由于辅助性 T 细胞（Th）对于针对抗原的抗体反应至关重要，因此我们采用了一种方法来绘制 NC16A 中的免疫显性 Th2 细胞表位。我们合成了 22 个重叠肽，涵盖了 BP180-NC16A 的整个序列，并使用酶联免疫斑点（ELISPOT）测定法研究了 BP 患者的 Th2 细胞对这些肽的反应性。我们筛选了两个表位肽，P2（492-506 aa：VRKLKARVDELERIR）和 P5（501-515 aa：ELERIRRSILPYGDS），并证实这些表位在刺激 CD4 T 细胞增殖和 Th2 白细胞介素-4（IL-4）细胞因子产生以及激活 B 细胞分泌自身抗体方面发挥主导作用。这些免疫显性表位受 HLA-DR 限制，并在具有不同 HLA 等位基因的受试者中观察到。这项工作有助于阐明 BP 的表位介导的免疫发病机制，并且鉴定出的 Th2 细胞表位是针对表位的特异性治疗策略的候选物。
