在一项新的研究中，来自英国、意大利、爱尔兰和荷兰的研究人员证实作为免疫系统的一个基础部分，自然杀伤细胞（NK细胞）能够通过单个被称作KIR2DS2的受体识别很多不同的病毒，包括全球性病原体，如寨卡病毒、登革热病毒和丙型肝炎病毒（HCV）。相关研究结果发表在2017年9月15日的Science Immunology期刊上，论文标题为“KIR2DS2 recognizes conserved peptides derived from viral helicases in the context of HLA-C”。
作者: ipsvirus 时间: 2017-9-24 14:18 KIR2DS2 recognizes conserved peptides derived from viral helicases in the context of HLA-C
Mohammed M. Naiyer1, Sorcha A. Cassidy1,2, Andrea Magri3,4, Vanessa Cowton3, Kevin Chen1, Salah Mansour1, Hariklia Kranidioti1, Berenice Mbirbindi1, Pauline Rettman1, Scott Harris5, Liam J. Fanning6, Arend Mulder7, Franz H. J. Claas7, Andrew D. Davidson8, Arvind H. Patel3, Marco A. Purbhoo2 and Salim I. Khakoo1,*
Killer cell immunoglobulin-like receptors (KIRs) are rapidly evolving species-specific natural killer (NK) cell receptors associated with protection against multiple different human viral infections. We report that the activating receptor KIR2DS2 directly recognizes viral peptides derived from conserved regions of flaviviral superfamily 2 RNA helicases in the context of major histocompatibility complex class I. We started by documenting that peptide LNPSVAATL from the hepatitis C virus (HCV) helicase binds HLA-C*0102, leading to NK cell activation through engagement of KIR2DS2. Although this region is highly conserved across HCV isolates, the sequence is not present in other flaviviral helicases. Embarking on a search for a conserved target of KIR2DS2, we show that HLA-C*0102 presents a different highly conserved peptide from the helicase motif 1b region of related flaviviruses, including dengue, Zika, yellow fever, and Japanese encephalitis viruses, to KIR2DS2. In contrast to LNPSVAATL from HCV, these flaviviral peptides all contain an “MCHAT” motif, which is present in 61 of 63 flaviviruses. Despite the difference in the peptide sequences, we show that KIR2DS2 recognizes endogenously presented helicase peptides and that KIR2DS2 is sufficient to inhibit HCV and dengue virus replication in the context of HLA-C*0102. Targeting short, but highly conserved, viral peptides provide nonrearranging innate immune receptors with an efficient mechanism to recognize multiple, highly variable, pathogenic RNA viruses.
