NK cell activation by KIR-binding antibody 1-7F9 and response to HIV-infected autologous cells in viremic and controller HIV-infected patients

• Published in: Clinical immunology (Orlando, Fla.) Fla.), 2010-02, Vol.134 (2), p.158-168
• Main Authors: Johansson, Susanne E, Hejdeman, Bo, Hinkula, Jorma, Johansson, Maria H, Romagné, François, Wahren, Britta, Wagtmann, Nicolai R, Kärre, Klas, Berg, Louise
• Format: Article
• Language: English
• Subjects: Adult; Allergy and Immunology; Antibodies, Monoclonal - immunology; Biological and medical sciences; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Genotype; HIV; HIV Infections - genetics; HIV Infections - immunology; HLA-C Antigens - genetics; HLA-C Antigens - immunology; Human immunodeficiency virus; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infectious diseases; Jurkat Cells; Killer Cells, Natural - immunology; Killer Cells, Natural - virology; KIR; Lymphocyte Activation - genetics; Lymphocyte Activation - immunology; Male; Medical sciences; MEDICIN; Medicin och hälsovetenskap; MEDICINE; Middle Aged; NK cell; Receptors, KIR - genetics; Receptors, KIR - immunology; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viremia; Viremic controller
• ISSN: 1521-6616; 1521-7035; 1521-7035
• DOI: 10.1016/j.clim.2009.10.001

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.