Steinsbø Øyvind, Henry Dunand Carole J, Huang Min, Mesin Luka, Salgado-Ferrer Marlene, Lundin Knut E A, Jahnsen Jørgen, Wilson Patrick C, Sollid Ludvig M
Centre for Immune Regulation and Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, 0372 Oslo, Norway.
Department of Medicine, Section of Rheumatology, Committee on Immunology, The Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, Illinois 60637, USA.
Nat Commun. 2014 Jun 9;5:4041. doi: 10.1038/ncomms5041.
Coeliac disease (CD), an enteropathy caused by cereal gluten ingestion, is characterized by CD4(+) T cells recognizing deamidated gluten and by antibodies reactive to gluten or the self-antigen transglutaminase 2 (TG2). TG2-specific immunoglobulin A (IgA) of plasma cells (PCs) from CD lesions have limited somatic hypermutation (SHM). Here we report that gluten-specific IgA of lesion-resident PCs share this feature. Monoclonal antibodies were expression cloned from single PCs of patients either isolated from cultures with reactivity to complex deamidated gluten antigen or by sorting with gluten peptide tetramers. Typically, the antibodies bind gluten peptides related to T-cell epitopes and many have higher reactivity to deamidated peptides. There is restricted VH and VL combination and usage among the antibodies. Limited SHM suggests that a common factor governs the mutation level in PCs producing TG2- and gluten-specific IgA. The antibodies have potential use for diagnosis of CD and for detection of gluten.
乳糜泻（CD）是一种由摄入谷物麸质引起的肠病，其特征在于CD4(+) T细胞识别脱酰胺麸质以及存在对麸质或自身抗原转谷氨酰胺酶2（TG2）有反应的抗体。来自CD病变部位浆细胞（PCs）的TG2特异性免疫球蛋白A（IgA）具有有限的体细胞超突变（SHM）。在此我们报告，病变部位驻留PCs的麸质特异性IgA也具有这一特征。单克隆抗体是从患者的单个PCs中通过表达克隆获得的，这些PCs要么是从对复杂脱酰胺麸质抗原具有反应性的培养物中分离出来的，要么是通过用麸质肽四聚体进行分选得到的。通常，这些抗体结合与T细胞表位相关的麸质肽，并且许多抗体对脱酰胺肽具有更高的反应性。抗体之间VH和VL的组合及使用受到限制。有限的SHM表明，一个共同因素控制着产生TG2特异性和麸质特异性IgA的PCs中的突变水平。这些抗体在CD诊断和麸质检测方面具有潜在用途。
