KIR2DS2 recognizes conserved peptides derived from viral helicases in the context of HLA-C

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Science Immunology  15 Sep 2017:
Vol. 2, Issue 15, eaal5296
DOI: 10.1126/sciimmunol.aal5296

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Killing viral helicases

Recognition of evolutionarily conserved pathogen-associated molecules drives innate immune responses. Naiyer et al. report that a killer cell immunoglobulin-like receptor (KIR), KIR2DS2, promotes activation of natural killer (NK) cells by recognizing conserved peptides from flaviviral RNA helicases when presented by a particular human leukocyte antigen (HLA) allele, HLA-C*0102. They have identified two distinct peptide motifs—LNPSVAATL and MCHAT—that are sensed by KIR2DS2. The former is conserved across hepatitis C virus isolates; the latter is conserved in a number of flaviviruses including dengue, Zika, and yellow fever viruses. The study illustrates that a single KIR receptor has evolved to activate NK cells in response to multiple pathogenic viruses.