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MAIT cell clonal expansion and TCR repertoire shaping in human volunteers challenged with Salmonella Paratyphi A.
Nature Communications ( IF 14.7 ) Pub Date : 2018-01-17 , DOI: 10.1038/s41467-017-02540-x
Lauren J Howson 1 , Giorgio Napolitani 1 , Dawn Shepherd 1, 2 , Hemza Ghadbane 1, 3 , Prathiba Kurupati 1 , Lorena Preciado-Llanes 1 , Margarida Rei 1 , Hazel C Dobinson 4 , Malick M Gibani 4 , Karen Wei Weng Teng 5 , Evan W Newell 5 , Natacha Veerapen 6 , Gurdyal S Besra 6 , Andrew J Pollard 4 , Vincenzo Cerundolo 1
Affiliation  

Mucosal-associated invariant T (MAIT) cells are innate-like T cells that can detect bacteria-derived metabolites presented on MR1. Here we show, using a controlled infection of humans with live Salmonella enterica serovar Paratyphi A, that MAIT cells are activated during infection, an effect maintained even after antibiotic treatment. At the peak of infection MAIT cell T-cell receptor (TCR)β clonotypes that are over-represented prior to infection transiently contract. Select MAIT cell TCRβ clonotypes that expand after infection have stronger TCR-dependent activation than do contracted clonotypes. Our results demonstrate that host exposure to antigen may drive clonal expansion of MAIT cells with increased functional avidity, suggesting a role for specific vaccination strategies to increase the frequency and potency of MAIT cells to optimize effector function.

中文翻译:


在遭受甲型副伤寒沙门氏菌攻击的人类志愿者中,MAIT 细胞克隆扩增和 TCR 库塑造。



粘膜相关不变 T (MAIT) 细胞是先天性 T 细胞,可以检测 MR1 上呈现的细菌衍生代谢物。在这里,我们通过用活的肠沙门氏菌甲型副伤寒血清型对人类进行控制感染,证明 MAIT 细胞在感染过程中被激活,即使在抗生素治疗后,这种效果仍然存在。在感染高峰期,感染前过度表达的 MAIT 细胞 T 细胞受体 (TCR)β 克隆型会短暂收缩。选择感染后扩增的 MAIT 细胞 TCRβ 克隆型比收缩的克隆型具有更强的 TCR 依赖性激活。我们的结果表明,宿主暴露于抗原可能会驱动 MAIT 细胞的克隆扩增,并增加功能亲和力,这表明特定的疫苗接种策略可以提高 MAIT 细胞的频率和效力,从而优化效应器功能。
更新日期:2018-01-17
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