Development of antibody-dependent cell cytotoxicity function in HIV-1 antibodies [article]

Laura E Doepker, Sonja Danon, Elias Harkins, Duncan Ralph, Zak Yaffe, Amrit Dhar, Cassia Wagner, Megan Stumpf, Dana Arenz, James A Williams, Walter Jaoko, Kishor Mandaliya (+3 others)
2020 bioRxiv   pre-print
A prerequisite for the design of an HIV vaccine that elicits protective antibodies is understanding the developmental pathways that result in desirable antibody features. The development of antibodies that mediate antibody-dependent cellular cytotoxicity (ADCC) is particularly relevant because such antibodies have been associated with HIV protection in humans. We reconstructed the developmental pathways of six human HIV-specific ADCC antibodies using longitudinal antibody sequencing data. Most
more » ... f the inferred naive antibodies did not mediate detectable ADCC. Gain of antigen binding and ADCC function typically required mutations in complementarity determining regions of one or both chains. Enhancement of ADCC potency often required additional mutations in framework regions. Antigen binding affinity and ADCC activity were correlated, but affinity alone was not sufficient to predict ADCC potency. Thus, elicitation of human ADCC antibodies may require mutations that first enable high affinity antigen recognition, followed by mutations that optimize factors contributing to functional ADCC activity.
doi:10.1101/2020.09.24.312066 fatcat:zh5v5jvncvbd7hlny5kjpl62ma