Ann Rheum Dis:狼疮抗原中T细胞表位的性质和HLA-DR决定了自身抗体的启动和多样性

2018-09-26 xiangting MedSci原创

狼疮相关自身抗原的独特抗原结构为作为靶标和T、B细胞表位扩散、自身抗体独特类型的多样化提供了基础。

已证明系统性红斑狼疮(SLE)相关自身抗体的产生是T细胞依赖性的,而抗原受到HLA-DR限制的驱动。这项研究探讨了起始抗原和自身抗体多样化的机制。

使用SmD和SmD重叠肽免疫的DR3+AE0小鼠产生的T-T杂交瘤定位SmD1(SmD)的T细胞表位(T-表位)。对来自反应性杂交瘤的TCRs进行测序。确定核心表位。通过生物信息学鉴定细菌模拟物。通过ELISA和免疫组化分析SmD肽免疫的DR3+AE0小鼠的血清及其模拟物的反应性。分析献血者样本的HLA-DR和自身抗体特异性。

确定了SmD内多个HLA-DR3限制性T表位。许多T-T杂交瘤与一个以上表位反应。其中一些与其他snRNP肽和Ro60/La/Ro52复合物蛋白有交叉反应。反应性杂交瘤使用独特的TCRs。在共生和环境细菌中鉴定出多个T表位模拟物。某些细菌模拟物与相关的SmD肽共享T和B细胞表位。细菌模拟物诱导产生狼疮相关抗原和不同组织的自身抗体。HLA-DR3+献血者的SLE相关性自身抗体显著较多。

狼疮相关自身抗原的独特抗原结构为作为靶标和T、B细胞表位扩散、自身抗体独特类型的多样化提供了基础。由于自身反应性T细胞的不完全阴性选择,SLE相关性自身抗体可能来自对共生和/或环境微生物的反应。在正常个体中SLE相关性抗体的产生是不可避免的。这项研究的结果对一般的自身免疫具有重要意义。

原始出处:

Zhenhuan Zhao. Nature of T cell epitopes in lupus antigens and HLA-DR determines autoantibody initiation and diversification. Ann Rheum Dis. 25 September 2018.

本文系梅斯医学(MedSci)原创译整理,转载需授权!

 

 

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    2018-10-06 1e145228m78(暂无匿称)

    学习了,谢谢作者分享!

    0

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    2018-09-28 marongnuan
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