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NK cell responses to cytomegalovirus infection lead to stable imprints in the human KIR repertoire and involve activating KIRs
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2013 (English)In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 121, no 14, 2678-2688 p.Article in journal (Refereed) Published
Abstract [en]

Human natural killer (NK) cells are functionally regulated by killer cell immunoglobulin-like receptors (KIRs) and their interactions with HLA class I molecules. As KIR expression in a given NK cell is genetically hard-wired, we hypothesized that KIR repertoire perturbations reflect expansions of unique NK-cell subsets and may be used to trace adaptation of the NK-cell compartment to virus infections. By determining the human KIR-ome at a single-cell level in more than 200 donors, we were able to analyze the magnitude of NK cell adaptation to virus infections in healthy individuals. Strikingly, infection with human cytomegalovirus (CMV), but not with other common herpesviruses, induced expansion and differentiation of KIR-expressing NK cells, visible as stable imprints in the repertoire. Education by inhibitory KIRs promoted the clonal-like expansion of NK cells, causing a bias for self-specific inhibitory KIRs. Furthermore, our data revealed a unique contribution of activating KIRs (KIR2DS4, KIR2DS2, or KIR3DS1), in addition to NKG2C, in the expansion of human NK cells. These results provide new insight into the diversity of KIR repertoire and its adaptation to virus infection, suggesting a role for both activating and inhibitory KIRs in immunity to CMV infection.

Place, publisher, year, edition, pages
2013. Vol. 121, no 14, 2678-2688 p.
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URN: urn:nbn:se:su:diva-92817DOI: 10.1182/blood-2012-10-459545ISI: 000321824100016OAI: diva2:642516
The Wenner-Gren FoundationWellcome trustSwedish Research Council


Available from: 2013-08-22 Created: 2013-08-20 Last updated: 2013-09-02Bibliographically approved

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Sohlberg, EbbaSverremark-Ekström, Eva
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Department of Molecular Biosciences, The Wenner-Gren Institute
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