title: 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 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.
authors: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden. vivien.beziat@ki.se
authors: Vivien
authors: V
authors: Béziat
authors: Lisa L
authors: LL
authors: Liu
authors: Jenny-Ann
authors: JA
authors: Malmberg
authors: Martin A
authors: MA
authors: Ivarsson
authors: Ebba
authors: E
authors: Sohlberg
authors: Andreas T
authors: AT
authors: Björklund
authors: Christelle
authors: C
authors: Retière
authors: Eva
authors: E
authors: Sverremark-Ekström
authors: James
authors: J
authors: Traherne
authors: Per
authors: P
authors: Ljungman
authors: Marie
authors: M
authors: Schaffer
authors: David A
authors: DA
authors: Price
authors: John
authors: J
authors: Trowsdale
authors: Jakob
authors: J
authors: Michaëlsson
authors: Hans-Gustaf
authors: HG
authors: Ljunggren
authors: Karl-Johan
authors: KJ
authors: Malmberg
mesh_terms: D002455:Cell Division / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000276:immunology*; D005434:Flow Cytometry; D006566:Herpesviridae Infections / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology* / Q000821:virology*; D008213:Lymphocyte Activation / Q000276:immunology; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000276:immunology / Q000378:metabolism; D054340:Receptors, KIR / Q000276:immunology* / Q000378:metabolism; D054349:Receptors, KIR3DS1 / Q000276:immunology* / Q000378:metabolism
chemical_list: C433932:KIR2DS2 protein, human; C473953:KIR2DS4 protein, human; C527059:KLRC2 protein, human; D055654:NK Cell Lectin-Like Receptor Subfamily C; D054340:Receptors, KIR; D054349:Receptors, KIR3DS1