来自流感的神秘MHC-E表位引起了强大的细胞分解性T细胞反应
Michael J Hogan1, Nikita Maheshwari2,3,4, Bridget E Begg5
1Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA. mihogan@upenn.edu.
Nature immunology
|October 12, 2023
概括
这项研究揭示了由MHC-E分子呈现的非传统病毒表位驱动CD8T细胞免疫力. 这些由替代翻译产生的神秘表位是mRNA疫苗的目标,并具有治疗潜力.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 分子生物学分子生物学
背景情况:
- CD8 T细胞通常通过经典的MHC I类 (MHC-Ia) 识别病毒表位.
- 非经典的MHC类Ib (MHC-Ib),与MHC-E一样,和神秘的表位呈现T细胞免疫的非常规目标.
- 这些非传统途径在抗病毒反应中的作用仍然在很大程度上是未知的.
研究的目的:
- 为了研究在流感病毒感染期间驱动T细胞免疫力的非传统抗原呈现.
- 识别新型病毒表位和它们的呈现途径.
- 探索针对这些非传统反应的治疗潜力.
主要方法:
- 采用免疫皮体学方法在感染流感A/波多黎各/8/1934的小鼠中识别病毒表位.
- 通过MHC-E (小鼠的Qa-1,人类的HLA-E) 鉴定出已知的表位的表现.
- 评估T细胞反应,包括细胞分解活性和记忆细胞分化,并评估mRNA疫苗的疗效.
主要成果:
- 鉴定了一种由Qa-1呈现的神秘病毒表位 (M-SL9),该表位来自于流感矩阵基因的替代阅读框架.
- 证明的M-SL9呈现和免疫性取决于泄漏的核糖体扫描和第二个AUG编码子.
- 观察到的M-SL9特异性T细胞分化为组织内存细胞,并在体内中介抗原特异性细胞解.
- 显示M-SL9特异性T细胞可以通过信使RNA疫苗接种来诱导.
结论:
- 非正典翻译产品可以对T细胞谱系做出重大贡献.
- 针对神秘病毒表位的MHC-E受限制的T细胞代表了抗病毒疗法的有希望的途径.
- 使者RNA疫苗接种策略可以有效地诱导T细胞对非传统表位的反应.
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