Conformational Plasticity in Broadly Neutralizing HIV-1 Antibodies Triggers Polyreactivity

Cell Reports
Julie PrigentHugo Mouquet

Abstract

Human high-affinity antibodies to pathogens often recognize unrelated ligands. The molecular origin and the role of this polyreactivity are largely unknown. Here, we report that HIV-1 broadly neutralizing antibodies (bNAbs) are frequently polyreactive, cross-reacting with non-HIV-1 molecules, including self-antigens. Mutating bNAb genes to increase HIV-1 binding and neutralization also results in de novo polyreactivity. Unliganded paratopes of polyreactive bNAbs with improved HIV-1 neutralization exhibit a conformational flexibility, which contributes to enhanced affinity of bNAbs to various HIV-1 envelope glycoproteins and non-HIV antigens. Binding adaptation of polyreactive bNAbs to the divergent ligands mainly involves hydrophophic interactions. Plasticity of bNAbs' paratopes may, therefore, facilitate accommodating divergent viral variants, but it simultaneously triggers promiscuous binding to non-HIV-1 antigens. Thus, a certain level of polyreactivity can be a mark of adaptable antibodies displaying optimal pathogens' recognition.

Citations

Apr 6, 2019·Transplantation·Emmanuel Zorn, Sarah B See
Jun 25, 2020·The Journal of Experimental Medicine·Verena HehleHugo Mouquet
Jun 26, 2020·The Journal of Clinical Investigation·Marina TuyishimeGuido Ferrari
Aug 29, 2020·Proceedings of the National Academy of Sciences of the United States of America·Deborah L BurnettDaniel Christ
Feb 7, 2019·The Biochemical Journal·Deepti Jain, Dinakar M Salunke
Oct 8, 2019·The Journal of Clinical Investigation·Jana BlazkovaTae-Wook Chun
Dec 4, 2019·Expert Review of Vaccines·Iván Del Moral-Sánchez, Kwinten Sliepen
Feb 6, 2019·Nature Reviews. Immunology·Alexia KanyavuzJordan D Dimitrov
Oct 21, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sofia RossiniJordan D Dimitrov
Apr 4, 2021·Viruses·Harry N White
Apr 27, 2020·Trends in Pharmacological Sciences·Jordan D Dimitrov
Jul 12, 2021·Trends in Immunology·Alejandra Reyes-Ruiz, Jordan D Dimitrov
Nov 6, 2021·Frontiers in Immunology·Sarah A Griffith, Laura E McCoy

❮ Previous
Next ❯

Methods Mentioned

BETA
ELISA
surface
surface plasmon resonance
chips
flow cytometry
fluorescence spectroscopy
X-ray

Software Mentioned

Modeler

Related Concepts

Related Feeds

Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.