Two Families of Env Antibodies Efficiently Engage Fc-Gamma Receptors and Eliminate HIV -1-Infected Cells

Sai Priya Anand, Jérémie Prévost, Sophie Baril, Jonathan Richard, Halima Medjahed, Jean Philippe Chapleau, William D. Tolbert, Sharon Kirk, Amos B. Smith, Bruce D. Wines, Stephen J. Kent, P. Mark Hogarth, Matthew S. Parsons, Marzena Pazgier, Andrés Finzi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

HIV -1 conceals epitopes of its envelope glycoproteins (Env) recognized by antibody (Ab)-dependent cellular cytotoxicity (ADCC)-mediating antibodies. These Abs, including anti-coreceptor binding site (CoRBS) and anti-cluster A antibodies, preferentially recognize Env in its "open" conformation. The binding of anti-CoRBS Abs has been shown to induce conformational changes that further open Env, allowing interaction of anti-cluster A antibodies. We explored the possibility that CoRBS Abs synergize with anti-cluster A Abs to engage Fc-gamma receptors to mediate ADCC. We found that binding of anti-CoRBS and anti-cluster A Abs to the same gp120 is required for interaction with soluble dimeric FcRIIIa in enzymelinked immunosorbent assays (ELISAs). We also found that Fc regions of both Abs are required to optimally engage FcRIIIa and mediate robust ADCC. Taken together, our results indicate that these two families of Abs act together in a sequential and synergistic fashion to promote FcRIIIa engagement and ADCC.

Original languageEnglish
Article numbere01823-18
JournalJournal of Virology
Volume93
Issue number3
DOIs
StatePublished - 1 Feb 2019
Externally publishedYes

Keywords

  • Adcc
  • Anti-cluster a antibodies
  • Anticoreceptor binding site antibodies
  • Cd4-mimetics
  • Env
  • Fcriiia
  • HIV -1
  • Nonneutralizing antibodies

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