Breaching Peripheral Tolerance Promotes the Production of HIV-1-neutralizing Antibodies

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2017 Jul 13

PMID 28698284

Citations 28

Authors

Kristin M S Schroeder

Amanda Agazio

Pamela J Strauch

Sean T Jones

Scott B Thompson

Michael S Harper

Roberta Pelanda

Mario L Santiago

Raul M Torres

Affiliations

Soon will be listed here.

Abstract

A subset of characterized HIV-1 broadly neutralizing antibodies (bnAbs) are polyreactive with additional specificities for self-antigens and it has been proposed immunological tolerance may present a barrier to their participation in protective humoral immunity. We address this hypothesis by immunizing autoimmune-prone mice with HIV-1 Envelope (Env) and characterizing the primary antibody response for HIV-1 neutralization. We find autoimmune mice generate neutralizing antibody responses to tier 2 HIV-1 strains with alum treatment alone in the absence of Env. Importantly, experimentally breaching immunological tolerance in wild-type mice also leads to the production of tier 2 HIV-1-neutralizing antibodies, which increase in breadth and potency following Env immunization. In both genetically prone and experimentally induced mouse models of autoimmunity, increased serum levels of IgM anti-histone H2A autoantibodies significantly correlated with tier 2 HIV-1 neutralization, and anti-H2A antibody clones were found to neutralize HIV-1. These data demonstrate that breaching peripheral tolerance permits a cross-reactive HIV-1 autoantibody response able to neutralize HIV-1.

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