仅限于DRB1*15:01的CD4 T细胞识别了两种能够进行细胞内抗原呈现的爱斯坦-巴尔病毒糖蛋白
Natalia Drosu1,2, Monique Anderson1, Philippe A Bilodeau1
1Department of Neurology, Division of Neuroimmunology & Neuroinfectious Disease, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114.
概括
人类白细胞抗原HLA-DR15,是多发性硬化症 (MS) 的遗传风险因素,驱动CD4 T细胞对gB和gH等爱斯坦-巴尔病毒 (EBV) 抗原的免疫力. 这将MS的环境和遗传因素联系在一起.
科学领域:
- 免疫学 免疫学 免疫学
- 遗传学 遗传学 是一个
- 病毒学 病毒学
背景情况:
- 多发性硬化症 (MS) 的风险涉及遗传和环境因素.
- 爱斯坦-巴尔病毒 (EBV) 感染是MS最强的环境风险因素.
- HLA-DR15是MS最强的遗传风险因素.
研究的目的:
- 研究对EBV的HLA-DR15受限免疫反应.
- 确定HLA-DR15如何通过EBV抗原影响CD4T细胞激活.
主要方法:
- 利用基于机器学习的HLA连接体预测来识别EBV表位.
- 用在体外测试中用于CD4 T细胞激活.
- 在B细胞中表达的复合EBV抗原,以评估T细胞的反应.
主要成果:
- 预计EBV糖蛋白B (gB) 表位体将通过HLA-DRB1*15:01.1呈现.
- 细胞内gB激活了CD4 T细胞,而这种方式取决于细胞内网膜 (ER) 贩运.
- 与非DR15对照组相比,HLA-DR15同卵性个体对EBV gB和gH的T细胞反应显著更高.
结论:
- HLA-DR15决定了CD4 T细胞对特定EBV抗原 (gB和gH) 的免疫力.
- 这提供了遗传风险因素HLA-DR15和环境风险因素EBV在MS病变发生过程中的机制联系.
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