Advertisement

 

 

Breaching peripheral tolerance promotes the production of HIV-1-neutralizing antibodies.

Breaching peripheral tolerance promotes the production of HIV-1-neutralizing antibodies.
Author Information (click to view)

Schroeder KMS, Agazio A, Strauch PJ, Jones ST, Thompson SB, Harper MS, Pelanda R, Santiago ML, Torres RM,


Schroeder KMS, Agazio A, Strauch PJ, Jones ST, Thompson SB, Harper MS, Pelanda R, Santiago ML, Torres RM, (click to view)

Schroeder KMS, Agazio A, Strauch PJ, Jones ST, Thompson SB, Harper MS, Pelanda R, Santiago ML, Torres RM,

Advertisement

The Journal of experimental medicine 2017 07 11() pii 10.1084/jem.20161190

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.

Submit a Comment

Your email address will not be published. Required fields are marked *

1 × 5 =

[ HIDE/SHOW ]