A Prominent Site of Antibody Vulnerability on HIV Envelope Incorporates a Motif Associated with CCR5 Binding and Its Camouflaging Glycans

Immunity. 2016 Jul 19;45(1):31-45. doi: 10.1016/j.immuni.2016.06.026.


The dense patch of high-mannose-type glycans surrounding the N332 glycan on the HIV envelope glycoprotein (Env) is targeted by multiple broadly neutralizing antibodies (bnAbs). This region is relatively conserved, implying functional importance, the origins of which are not well understood. Here we describe the isolation of new bnAbs targeting this region. Examination of these and previously described antibodies to Env revealed that four different bnAb families targeted the (324)GDIR(327) peptide stretch at the base of the gp120 V3 loop and its nearby glycans. We found that this peptide stretch constitutes part of the CCR5 co-receptor binding site, with the high-mannose patch glycans serving to camouflage it from most antibodies. GDIR-glycan bnAbs, in contrast, bound both (324)GDIR(327) peptide residues and high-mannose patch glycans, which enabled broad reactivity against diverse HIV isolates. Thus, as for the CD4 binding site, bnAb effectiveness relies on circumventing the defenses of a critical functional region on Env.

Publication types

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

MeSH terms

  • Amino Acid Motifs
  • Antibodies, Neutralizing / immunology*
  • Binding Sites, Antibody / immunology*
  • CD4 Antigens / metabolism
  • Epitope Mapping
  • Epitopes / metabolism
  • Genetic Engineering
  • HEK293 Cells
  • HIV Antibodies / immunology*
  • HIV Envelope Protein gp120 / immunology
  • HIV Envelope Protein gp120 / metabolism*
  • HIV Infections / immunology*
  • HIV-1 / immunology*
  • Humans
  • Immunity, Humoral
  • Immunologic Memory
  • Peptide Fragments / metabolism
  • Polysaccharides / immunology
  • Polysaccharides / metabolism*
  • Protein Binding
  • Receptors, CCR5 / metabolism


  • Antibodies, Neutralizing
  • CCR5 protein, human
  • CD4 Antigens
  • Epitopes
  • HIV Antibodies
  • HIV Envelope Protein gp120
  • Peptide Fragments
  • Polysaccharides
  • Receptors, CCR5
  • gp120 protein, Human immunodeficiency virus 1