The Fc Domain of Immunoglobulin Is Sufficient to Bridge NK Cells with Virally Infected Cells

Hong Sheng Dai, Nathaniel Griffin, Chelsea Bolyard, Hsiaoyin Charlene Mao, Jianying Zhang, Timothy P. Cripe, Tadahiro Suenaga, Hisashi Arase, Ichiro Nakano, E. A. Chiocca, Balveen Kaur, Jianhua Yu, Michael A. Caligiuri

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


Clearance of pathogens or tumor cells by antibodies traditionally requires both Fab and Fc domains of IgG. Here, we show the Fc domain of IgG alone mediates recognition and clearance of herpes simplex virus (HSV1)-infected cells. The human natural killer (NK) cell surface is naturally coated with IgG bound by its Fc domain to the Fcγ receptor CD16a. NK cells utilize the Fc domain of bound IgG to recognize gE, an HSV1-encoded glycoprotein that also binds the Fc domain of IgG but at a site distinct from CD16a. The bridge formed by the Fc domain between the HSV1-infected cell and the NK cell results in NK cell activation and lysis of the HSV1-infected cell in the absence of HSV1-specific antibody in vitro and prevents fatal HSV1 infection in vivo. This mechanism also explains how bacterial IgG-binding proteins regulate NK cell function and may be broadly applicable to Fcγ-receptor-bearing cells. IgG conventionally utilizes its Fab and Fc domains to engage antigens and immune effector cells, respectively. Dai et al. show that the Fc domain alone allows CD16+ NK cells to recognize and lyse virus-infected cells that express IgG-binding proteins.

Original languageEnglish (US)
Pages (from-to)159-170.e10
Issue number1
StatePublished - Jul 18 2017
Externally publishedYes


  • ADCC
  • CD16a
  • FcBCC
  • HSV1
  • NK cells
  • gE
  • herpes virus
  • protein A
  • protein G

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases


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