Abstract
BackgroundHIV-specific Antibody Dependent Cell Cytotoxicity (ADCC) has shown to be important in HIV control and resistance. The ADCC is mediated primarily by natural killer cell activated through the binding of FcγRIIIa receptor to the Fc portion of antibody bound to the antigen expressed on the infected cells. However, no data is available on the influence of the polymorphism in FcγRIIIa receptor on HIV-specific ADCC response.MethodsThe Sanger’s method of sequencing was used to sequence the exon of FcγRIIIa receptor while the ADCC activity was determined using NK cell activation assay. The polymorphism in FcγRIIIa receptor was assessed in HIV-infected Indian individuals with or without HIV-specific ADCC antibodies and its influence on the magnitude of HIV-specific ADCC responses was analyzed.ResultsTwo polymorphisms: V176F (rs396991) and Y158H (rs396716) were observed. The Y158H polymorphism is reported for the first time in Indian population. Both, V176F (V/V genotype) (p = 0.004) and Y158H (Y/H genotype) (p = 0.032) were found to be significantly associated with higher magnitude of HIV-specific ADCC response.ConclusionThe study underscores the role of polymorphism in the FcγRIIIa receptor on HIV-specific ADCC response and suggests that the screening of the individuals for FcγRIIIa-V176F and Y158H polymorphisms could be useful for prediction of efficient treatment in monoclonal antibody-based therapies aimed at ADCC in HIV infection.
Highlights
Human Immunodeficiency Virus (HIV)-specific Antibody Dependent Cell Cytotoxicity (ADCC) has shown to be important in HIV control and resistance
HIV-specific ADCC responses HIV-specific natural killer (NK) cell activation in presence of anti-HIV antibodies was used as a surrogate marker for HIV-specific ADCC response by number of studies [3, 4, 22,23,24,25,26]
No association of NK cell activation was observed with either CD4 count or viral loads. (Data not shown) The functionality of NK cells is known to be compromised in HIV infection [27, 28]
Summary
HIV-specific Antibody Dependent Cell Cytotoxicity (ADCC) has shown to be important in HIV control and resistance. The ADCC is mediated primarily by natural killer cell activated through the binding of FcγRIIIa receptor to the Fc portion of antibody bound to the antigen expressed on the infected cells. The ADCC is mediated primarily by natural killer (NK) cells through binding of the FcγRIIIa (CD16a) receptor with the Fc portion of the antibodies bound to the specific antigen expressed on the target cells. This binding initiates secretion of granzyme and perforin by NK cells resulting in the lysis of the target cell [7]. Y158H has shown possibility of association with HIV acquisition
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