NK cell activation by KIR-binding antibody 1-7F9 and response to HIV-infected autologous cells in viremic and controller HIV-infected patients |
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Authors: | Susanne E. Johansson,Bo Hejdeman,Jorma Hinkula,Maria H. Johansson,Franç ois Romagné ,Britta Wahren,Nicolai R. Wagtmann,Klas Kä rre,Louise Berg |
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Affiliation: | 1. Department of Microbiology, Tumor and Cell Biology and Strategic Research Center IRIS, Karolinska Institutet, Stockholm, Sweden;2. Swedish Institute for Infectious Disease Control, Stockholm, Sweden;3. Venhälsan, South Hospital, Stockholm, Sweden;4. Department of Molecular Virology, Linköping University, Linköping, Sweden;5. Innate Pharma, Marseille, France;6. NovoNordisk, Bagsværd, Denmark |
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Abstract: | Natural killer (NK) cells may be protective in HIV infection and are inhibited by killer cell immunoglobulin-like receptors (KIRs) interacting with MHC class I molecules, including HLA-C. Retention of HLA-C despite downregulation of other MHC class I molecules on HIV infected cells might protect infected cells from NK cell recognition in vitro. To assess the role of inhibitory HLA-C ligands in the capacity of NK cells to recognize autologous infected T cells, we measured NK cell degranulation in vitro in viremic patients, controllers with low viremia, and healthy donors. No difference in NK cell response to uninfected compared to HIV-1IIIB infected targets was observed. Activation of NK cells was regulated by KIRs, because NK cell degranulation was increased by 1-7F9, a human antibody that binds KIR2DL1/L2/L3 and KIR2DS1/S2, and this effect was most pronounced in KIR haplotype B individuals. |
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Keywords: | NK cell HIV KIR Viremic controller |
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