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B-103 Fc Bridged Cellular Cytotoxicity (FcBCC): A novel mechanism by which NK cells recognize HSV

Dai, Hongsheng, PhD; Caligiuri, Michael, A., MD*

JAIDS Journal of Acquired Immune Deficiency Syndromes: April 2018 - Volume 77 - Issue - p 36
doi: 10.1097/01.qai.0000532584.98565.bf
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The initial infection by herpes simplex virus 1 (HSV1) is usually a self-limited event, but the mechanism of this protection prior to the development of a primary humoral response is unknown. Individuals deficient in natural killer (NK) cells can suffer from overwhelming and at times fatal HSV1 infection. The NK cell surface is naturally coated with IgG that is bound to Fcγ receptor CD16a. Here we show that human NK cells utilize the Fc portion of IgG bound to its cell surface to recognize gE, an HSV1-encoded glycoprotein that also binds the Fc portion of IgG but at a site distinct from that of CD16a. The Fc-bridge formed between the HSV1-infected cell and the NK cell results in NK cell activation and spontaneous lysis of the HSV-infected cell in the absence of HSV-specific antibody. In vivo, the absence of the Fc portion of human IgG, or of NK cells, results in death from primary HSV1 infection. This mechanism, which we call Fc bridged cellular cytotoxicity (FcBCC) may be broadly applicable to Fcγ receptor-bearing immune cells and other pathogens encoding Fc-binding proteins.

*The Ohio State University Comprehensive Cancer Center; The James Cancer Hospital and Solove Research Institute, Columbus Ohio

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