Lab Medicine

Immune System Targets Diverse Viruses Using the Same Small Peptide

KNOW YOUR ENEMY: Natural killer cells, like the one attacking this larger cancer cell, can be activated by cell-surface receptors called activating KIRs. GWENOLINE BORHIS

The paper
M.M. Naiyer, “KIR2DS2 recognizes conserved peptides derived from viral helicases in the context of HLA-C,” Science Immunology, 2:eaal5296, 2017.

Killing machines
Natural killer (NK) cells help fight viral infections as part of the body’s innate immune response. Activation of these cells depends partly on a set of NK cell-surface proteins called activating killer cell immunoglobulin-like receptors (KIRs). But how activating KIRs recognize pathogens is poorly understood.

Searching for a match
While screening for viral peptides that stimulate one receptor, KIR2DS2, hepatologist Salim Khakoo’s group at the University of Southampton, U.K., stumbled across an amino acid sequence that appears highly conserved across multiple flaviviruses, from Zika to Japanese encephalitis. “There are about 63 different flaviviruses, and they almost all have this five-amino-acid sequence,” says Khakoo. “We were absolutely astonished.”

One size fits all
Using human cell lines, the team showed that major histocompatibility complex proteins—important components of the vertebrate immune system—on virus-infected cells present this sequence to KIR2DS2, which then activates NK cells to inhibit viral replication. The fact that multiple viruses stimulate the same receptor suggests the possibility of developing broadly antiviral therapeutics, Khakoo says. “We’re working on ways of using this knowledge to activate natural killer cells, and develop a natural killer cell–based vaccine strategy.”

Out of lines
KIR researcher Marcus Altfeld of the Leibniz Institute for Experimental Virology in Germany says he’s impressed by the study’s description of KIR2DS2’s mechanism of action. However, he notes, “cell lines create a bit of an artificial system. . . . The next challenge will be to see whether these responses can be seen in cells from a patient.”

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