An autoreactive antibody from an SLE/HIV-1 individual broadly neutralizes HIV-1

J Clin Invest. 2014 Apr;124(4):1835-43. doi: 10.1172/JCI73441. Epub 2014 Mar 10.

Abstract

Broadly HIV-1-neutralizing antibodies (BnAbs) display one or more unusual traits, including a long heavy chain complementarity-determining region 3 (HCDR3), polyreactivity, and high levels of somatic mutations. These shared characteristics suggest that BnAb development might be limited by immune tolerance controls. It has been postulated that HIV-1-infected individuals with autoimmune disease and defective immune tolerance mechanisms may produce BnAbs more readily than those without autoimmune diseases. In this study, we identified an HIV-1-infected individual with SLE who exhibited controlled viral load (<5,000 copies/ml) in the absence of controlling HLA phenotypes and developed plasma HIV-1 neutralization breadth. We collected memory B cells from this individual and isolated a BnAb, CH98, that targets the CD4 binding site (CD4bs) of HIV-1 envelope glycoprotein 120 (gp120). CH98 bound to human antigens including dsDNA, which is specifically associated with SLE. Anti-dsDNA reactivity was also present in the patient's plasma. CH98 had a mutation frequency of 25% and 15% nt somatic mutations in the heavy and light chain variable domains, respectively, a long HCDR3, and a deletion in the light chain CDR1. The occurrence of anti-dsDNA reactivity by a HIV-1 CD4bs BnAb in an individual with SLE raises the possibility that some BnAbs and SLE-associated autoantibodies arise from similar pools of B cells.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Antibodies, Antinuclear / blood
  • Antibodies, Antinuclear / chemistry
  • Antibodies, Antinuclear / genetics
  • Antibodies, Neutralizing / blood*
  • Antibodies, Neutralizing / chemistry
  • Antibodies, Neutralizing / genetics
  • Autoantibodies / blood*
  • Autoantibodies / chemistry
  • Autoantibodies / genetics
  • B-Lymphocytes / immunology
  • Base Sequence
  • DNA / genetics
  • Female
  • HIV Antibodies / blood*
  • HIV Antibodies / chemistry
  • HIV Antibodies / genetics
  • HIV Envelope Protein gp120 / chemistry
  • HIV Envelope Protein gp120 / immunology
  • HIV Infections / complications*
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV-1 / immunology*
  • Humans
  • Immunologic Memory
  • Lupus Erythematosus, Systemic / complications*
  • Lupus Erythematosus, Systemic / immunology*
  • Models, Molecular
  • Molecular Sequence Data
  • Multiprotein Complexes / chemistry
  • Mutation
  • Protein Conformation
  • Sequence Homology, Amino Acid
  • Sequence Homology, Nucleic Acid
  • Viral Load

Substances

  • Antibodies, Antinuclear
  • Antibodies, Neutralizing
  • Autoantibodies
  • HIV Antibodies
  • HIV Envelope Protein gp120
  • Multiprotein Complexes
  • gp120 protein, Human immunodeficiency virus 1
  • DNA

Associated data

  • PDB/3NGB
  • PDB/4JAN