title: NKG2A-Expressing Natural Killer Cells Dominate the Response to Autologous Lymphoblastoid Cells Infected with Epstein-Barr Virus.
abstract: Epstein-Barr virus (EBV) is a human γ-herpesvirus that establishes latency and lifelong infection in host B cells while achieving a balance with the host immune response. When the immune system is perturbed through immunosuppression or immunodeficiency, however, these latently infected B cells can give rise to aggressive B cell lymphomas. Natural killer (NK) cells are regarded as critical in the early immune response to viral infection, but their role in controlling expansion of infected B cells is not understood. Here, we report that NK cells from healthy human donors display increased killing of autologous B lymphoblastoid cell lines (LCLs) harboring latent EBV compared to primary B cells. Coculture of NK cells with autologous EBV+LCL identifies an NK cell population that produces IFNγ and mobilizes the cytotoxic granule protein CD107a. Multi-parameter flow cytometry and Boolean analysis reveal that these functional cells are enriched for expression of the NK cell receptor NKG2A. Further, NKG2A+NK cells more efficiently lyse autologous LCL than do NKG2A-NK cells. More specifically, NKG2A+2B4+CD16-CD57-NKG2C-NKG2D+cells constitute the predominant NK cell population that responds to latently infected autologous EBV+B cells. Thus, a subset of NK cells is enhanced for the ability to recognize and eliminate autologous, EBV-infected transformed cells, laying the groundwork for harnessing this subset for therapeutic use in EBV+malignancies.
authors.affiliation: Department of Molecular Biology, Colorado College, Colorado Springs, CO, USA; Program in Immunology, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Olivia
authors.initials: O
authors.lastname: Hatton
authors.affiliation: Program in Immunology, Stanford University School of Medicine , Stanford, CA , USA.
authors.forename: Dara Marie
authors.initials: DM
authors.lastname: Strauss-Albee
authors.affiliation: Program in Immunology, Stanford University School of Medicine , Stanford, CA , USA.
authors.forename: Nancy Q
authors.initials: NQ
authors.lastname: Zhao
authors.affiliation: Program in Immunology, Stanford University School of Medicine , Stanford, CA , USA.
authors.forename: Mikel D
authors.initials: MD
authors.lastname: Haggadone
authors.affiliation: Program in Immunology, Stanford University School of Medicine , Stanford, CA , USA.
authors.forename: Judith Shanika
authors.initials: JS
authors.lastname: Pelpola
authors.affiliation: Program in Immunology, Stanford University School of Medicine, Stanford, CA, USA; Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Sheri M
authors.initials: SM
authors.lastname: Krams
authors.affiliation: Program in Immunology, Stanford University School of Medicine, Stanford, CA, USA; Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Olivia M
authors.initials: OM
authors.lastname: Martinez
authors.affiliation: Program in Immunology, Stanford University School of Medicine, Stanford, CA, USA; Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Blish
keywords: B cells; Epstein–Barr virus; NK cells; NKG2A; lymphoblastoid cell lines