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NK cell responses to cytomegalovirus infection lead to stable imprints in the human KIR repertoire and involve activating KIRs

Abstract : 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 expressionin a given NK cell is genetically hard-wired, we hypothesized that KIR repertoire per-turbations reflect expansions of unique NK-cell subsets and may be used to traceadaptation 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 themagnitude 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 im-prints in the repertoire. Education by inhibitory KIRs promoted the clonal-like expansion ofNK cells, causing a bias for self-specific inhibitory KIRs. Furthermore, our data revealeda unique contribution of activating KIRs (KIR2DS4, KIR2DS2, or KIR3DS1), in addition toNKG2C, in the expansion of human NK cells. These results provide new insight into thediversity of KIR repertoire and its adaptation to virus infection, suggesting a role for bothactivating and inhibitory KIRs in immunity to CMV infection.
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https://www.hal.inserm.fr/inserm-03291382
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Submitted on : Monday, July 19, 2021 - 5:12:04 PM
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Vivien Béziat, Lisa Liu, Jenny-Ann Malmberg, Martin Ivarsson, Ebba Sohlberg, et al.. NK cell responses to cytomegalovirus infection lead to stable imprints in the human KIR repertoire and involve activating KIRs. Blood, American Society of Hematology, 2013, 121 (14), pp.2678-2688. ⟨10.1182/blood-2012-10-459545⟩. ⟨inserm-03291382⟩

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