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首页> 外文期刊>Infection and immunity >T-Cell-Dependent Antibody Response to the Dominant Epitope of Streptococcal Polysaccharide,N-Acetyl-Glucosamine, Is Cross-Reactive with Cardiac Myosin
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T-Cell-Dependent Antibody Response to the Dominant Epitope of Streptococcal Polysaccharide,N-Acetyl-Glucosamine, Is Cross-Reactive with Cardiac Myosin

机译：对链球菌多糖N-乙酰氨基葡萄糖的主要抗原决定簇的T细胞依赖性抗体反应与心肌肌球蛋白交叉反应

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Autoantibodies against myosin are associated with myocarditis and rheumatic heart disease. In this study, the antigenic cross-reactivity of myosin and N-acetyl-glucosamine (GlcNAc), the dominant epitope of Group A streptococcal polysaccharide, was examined. Six antimyosin monoclonal antibodies (MAbs) derived from mice with cardiac myosin-induced myocarditis were characterized. All MAbs cross-reacted with GlcNAc, mimicking a subset of MAbs derived from rheumatic carditis patients that bind both myosin and streptococcal polysaccharide. Variable (V) region gene usage was diverse, with five of six MAb heavy-chain V regions encoded by distinct members of the J558 family and the sixth encoded by a member of the VGAM3.8 family. Light-chain V-region segments were derived from the Vk1, Vk4/5, Vk10, and Vk21 families. These antimyosin, anti-GlcNac MAbs demonstrated several T-cell-dependent features: they were predominantly immunoglobulin G, were encoded by V-region genes expressed late in development, and displayed somatic mutation. A direct correlation between the extent of somatic mutation and the affinity for myosin was observed. Affinity for GlcNAc also increased with the frequency of mutation, demonstrating that affinity maturation can occur simultaneously for both self antigen and foreign antigen. Based on these observations, we immunized mice with GlcNAc coupled to bovine serum albumin and demonstrated that a T-cell-dependent response to GlcNAc leads to antimyosin reactivity. We speculate that the pathogenic antibody response in rheumatic carditis may reflect the conversion of a T-cell-independent response to GlcNAc to a T-cell-dependent cross-reactive response to GlcNAc and myosin.
机译：抗肌球蛋白的自身抗体与心肌炎和风湿性心脏病有关。在这项研究中，检查了肌球蛋白和 N -乙酰基-葡糖胺（GlcNAc）（A组链球菌多糖的主要表位）的抗原交叉反应性。表征了源自患有心肌肌球蛋白诱导的心肌炎的小鼠的六种抗肌球蛋白单克隆抗体（MAb）。所有单克隆抗体均与GlcNAc发生交叉反应，模仿了类风湿性心脏病患者的一部分单克隆抗体，该个体同时结合了肌球蛋白和链球菌多糖。可变（V）区基因的用法是多种多样的，六个MAb重链V区中的五个由J558家族的不同成员编码，第六个由VGAM3.8家族的成员编码。轻链V区片段来自Vk1，Vk4 / 5，Vk10和Vk21家族。这些抗肌球蛋白，抗GlcNac MAb表现出一些T细胞依赖性特征：它们主要是免疫球蛋白G，由发育后期表达的V区基因编码，并显示出体细胞突变。观察到体细胞突变的程度和对肌球蛋白的亲和力之间存在直接相关性。对GlcNAc的亲和力也随着突变频率的增加而增加，这表明自身抗原和外源抗原均可同时发生亲和力成熟。基于这些观察结果，我们用与牛血清白蛋白偶联的GlcNAc免疫了小鼠，并证明了对GlcNAc的T细胞依赖性反应导致抗肌球蛋白反应性。我们推测风湿性心脏病的病原性抗体反应可能反映了对GlcNAc的T细胞非依赖性反应向对GlcNAc和肌球蛋白的T细胞非依赖性反应的转化。

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