Type 2 T-Cell Responses against Distinct Epitopes of the Desmoglein 3 Ectodomain in Pemphigus Vulgaris

Dario Didona, Luca Scarsella,Christoph Hudemann, Karolin Volkmann, Christine L. Zimmer,Benedikt Beckert, Ritva Tikkanen,Vera Korff, Katja Kuehn,Sandra Wienzek-Lischka, Gregor Bein,Giovanni Di Zenzo, Jaqueline Boehme,Tomas Cunha, Farzan Solimani,Josquin Pieper, Hazem A. Juratli,Manuel Goebel, Thomas Schmidt,Luca Borradori, Amir S. Yazdi,Cassian Sitaru,Holger Garn, Rudiger Eming, Sabine Fleischer,Michael Hertl

JOURNAL OF INVESTIGATIVE DERMATOLOGY(2024)

引用 0|浏览12
暂无评分
摘要
Pemphigus vulgaris (PV) is an autoimmune blistering disorder of the skin and/or mucous membranes caused by IgG autoantibodies that predominantly target two transmembrane desmosomal cadherins: desmoglein (DSG)1 and DSG3. DSG-specific T cells play a central role in PV pathogenesis because they provide help to autoreactive B cells for autoantibody production. In this study, we characterized DSG3-specific peripheral T cells in a cohort of 52 patients with PV and 41 healthy controls with regard to cytokine profile and epitope specificity. By ELISpot analysis, type 2 T cells reactive with the DSG3 ectodomain were significantly increased in patients with PV compared with those in healthy controls. By dextramer analysis, CD4 thorn T cells specific for an epitope within the extracellular domain of DSG3, DSG3(206-220), were found at significantly higher frequencies in patients with PV than in HLA-matched healthy controls. T-cell recognition of two distinct DSG3 epitopes, that is, DSG3(206-220) and DSG3(378-392), correlated significantly, suggesting a synergistic effect in B-cell help. Immunization of HLADRB1*04:02-transgenic mice with PV with the same set of DSG3 peptides induced pathogenic DSG3-specific IgG antibodies, which induced loss of keratinocyte adhesion in vitro. Thus, DSG3 peptide-specific T cells are of particular interest as surrogate markers of disease activity and potential therapeutic targets in PV.
更多
查看译文
关键词
CLIP,DSG,HC,MHC,PV,Th
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要