Identification of cardiac myosin peptides capable of inducing autoimmune myocarditis in BALB/c mice
Identification of cardiac myosin peptides capable of inducing autoimmune myocarditis in BALB/c mice
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DOI：
10.1172/jci118642
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发表时间：
1996-05-01
影响因子：
15.9
通讯作者：
Neu, N
中科院分区：
文献类型：
--
作者：
Pummerer, CL;Luze, K;Neu, N
用心肌肌球蛋白免疫遗传易感小鼠诱发T细胞介导的心肌炎，并作为自身免疫性心脏病的模型。本研究通过比较心肌肌球蛋白（α-）和比目鱼肌球蛋白（β-）的致病性，来鉴定肌球蛋白分子上的致病性表位。我们发现，α-肌球蛋白是免疫显性亚型酸诱导心肌炎的严重程度和患病率高，而β-肌球蛋白引起的疾病很少。因此，α-肌球蛋白的免疫优势表位必须位于α-和β-肌球蛋白异构体之间的不同氨基酸序列的区域，合成了对应于这些差异区域的心肌肌球蛋白肽，并测试了它们诱导炎性心脏病的能力，鉴定了三种致病肽。位于分子头部的一种肽诱导严重的心肌炎，而位于杆部分的另外两种肽仅具有轻微的致病性，心肌肌球蛋白分子上致病性表位的鉴定将允许详细研究免疫系统对该抗原的识别，并可能用于下调正在进行的心脏疾病。
Immunization with cardiac myosin induces T cell-mediated myocarditis in genetically predisposed mice and serves as a model for autoimmune heart disease, This study was under-taken to identify pathogenic epitopes on the myosin molecule, Our approach was based on the comparison of the pathogenicity between cardiac (alpha-) myosin and soleus muscle (beta-) myosin. We show that alpha-myosin is the immunodominant isoform acid induces myocarditis at high severity and prevalence whereas; beta-myosin induces little disease. Therefore the immunodominant epitopes of alpha-myosin must reside in regions of different amino acid sequence between alpha- and beta-myosin isoforms, Cardiac myosin peptides corresponding to these regions of difference were synthesized and tested for their ability to induce inflammatory heart disease, Three pathogenic peptides were identified. One peptide that is located in the head portion of the molecule induced severe myocarditis, whereas two others that reside in the rod portion possessed only minor pathogenicity, The identification of pathogenic epitopes on the cardiac myosin molecule will allow detailed studies on the recognition of this antigen by the immune system and might be used to downmodulate ongoing heart disease.