Alvarez et al.
Feb 23, 2017
This study investigates the Fc-gamma receptor (FCGR) activation profiles of IgG antibodies (Abs) from HIV viremic controllers (VCs) and how they contribute to immune responses against HIV.
This study investigates the Fc-gamma receptor (FCGR) activation profiles of IgG antibodies (Abs) from HIV viremic controllers (VCs) and how they contribute to immune responses against HIV. The researchers assessed IgG-mediated activation of FCGR2A and FCGR3A, key receptors involved in immune responses such as antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cell-mediated viral inhibition (ADCVI).
Key findings:
Enhanced FCGR Signaling: IgG from VCs, who naturally control HIV without antiretroviral therapy, exhibited significantly enhanced activation of FCGR2A and FCGR3A compared to chronically infected patients (CIPs) on antiretroviral therapy (ART). This enhanced signaling was independent of the magnitude of HIV-specific binding or neutralization.
No Difference in Neutralization: There were no significant differences in HIV neutralization capacity between VCs and CIPs, suggesting that enhanced FCGR signaling, rather than neutralization, may contribute to effective immune control in VCs.
Predictive Marker for VC Status: The enhanced FCGR activation was a strong predictor of VC status, with multivariate regression analysis showing that this feature could distinguish VCs from CIPs. Unsupervised clustering of IgG profiles also highlighted the distinct FCGR activation patterns in VCs.
Implications for Vaccine Development: This study suggests that profiling FCGR activation may be a useful approach for identifying protective HIV-specific IgG responses, potentially aiding in the design of more effective HIV vaccines.
In conclusion, the study highlights that enhanced FCGR signaling is a key feature of IgG from HIV controllers, contributing to their ability to control the virus and offering a potential target for improving HIV vaccine strategies.