How an autoimmune reaction triggered by molecular mimicry between streptococcal M protein and cardiac tissue proteins leads to heart lesions in rheumatic heart disease
How an autoimmune reaction triggered by molecular mimicry between streptococcal M protein and cardiac tissue proteins leads to heart lesions in rheumatic heart disease
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DOI：
10.1016/j.jaut.2005.01.007
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发表时间：
2005-03-01
影响因子：
12.8
通讯作者：
Guilherme, L
中科院分区：
文献类型：
--
作者：
Faé, KC;Oshiro, SE;Guilherme, L
微生物抗原和宿主组织之间的分子模拟被认为是感染后自身免疫性疾病的一种机制。在目前的工作中，我们描述了两个严重的风湿性心脏病（RHD）患者的自身免疫反应，通过分析心脏浸润的T细胞库，抗原识别，和细胞因子的产生诱导的特异性抗原。来自心脏寡克隆扩增T细胞的T细胞克隆交叉识别M5肽、心脏组织衍生蛋白和肌球蛋白肽。我们表明，使用结合亲和力测定，免疫显性链球菌肽（M5（81-96））是能够结合到HLA-DR 53分子。同样的肽被来自携带HLADR 15、DR 7和DR 53分子的患者的浸润性T细胞克隆识别。这表明该肽可能在HLA-DR 53分子的背景下呈递给T细胞。由M5蛋白及其肽和心脏组织衍生蛋白激活的交叉反应性心脏浸润T细胞主要产生炎性细胞因子。白细胞介素（IL）-4产生少量的二尖瓣病变内T细胞系和克隆。总之，这些结果表明，链球菌抗原和心脏组织蛋白之间的模仿，结合高炎症细胞因子和低IL-4的产生，导致自身免疫反应和心脏组织损伤的RHD患者的发展。(c)2005爱思唯尔有限公司保留所有权利。
Molecular mimicry between microbial antigens' and host tissue is suggested as a mechanism for post-infectious autoimmune disease. In the present work we describe the autoimmune reactions of two severe rheumatic heart disease (RHD) patients, through an analysis of heart-infiltrating T-cell repertoire, antigen recognition, and cytokine production induced by specific antigens. T-cell clones derived from oligoclonally expanded T cells in the heart cross-recognized M5 peptides, heart tissue-derived proteins, and myosin peptides. We show, using binding affinity assays, that an immunodominant streptococcal peptide (M5(81-96)) is capable of binding to the HLA-DR53 molecule. The same peptide was recognized by an infiltrating T-cell clone from a patient carrying HLADR 15, DR7, and DR53 molecules. This suggests that this peptide is probably presented to T cells in the context of the HLA-DR53 molecule. Cross-reactive heart-infiltrating T cells activated by the M5 protein and its peptides and by heart tissue-derived proteins produced predominantly inflammatory cytokines. Interteukin (IL)-4 was produced in small amounts by mitral valve intralesional T-cell lines and clones. Altogether, these results suggest that mimicry between streptococcal antigens and heart-tissue proteins, combined with-high inflammatory cytokine and low IL-4 production, leads to the development of autoimmune reactions and cardiac tissue damage in RHD patients. (c) 2005 Elsevier Ltd. All rights reserved.