Immunogenicity of membrane-bound HIV-1 gp41 membrane-proximal external region (MPER) segments is dominated by residue accessibility and modulated by stereochemistry.

Journal Article (Journal Article)

Structural characterization of epitope-paratope pairs has contributed to the understanding of antigenicity. By contrast, few structural studies relate to immunogenicity, the process of antigen-induced immune responses in vivo. Using a lipid-arrayed membrane-proximal external region (MPER) of HIV-1 glycoprotein 41 as a model antigen, we investigated the influence of physicochemical properties on immunogenicity in relation to structural modifications of MPER/liposome vaccines. Anchoring the MPER to the membrane via an alkyl tail or transmembrane domain retained the MPER on liposomes in vivo, while preserving MPER secondary structure. However, structural modifications that affected MPER membrane orientation and antigenic residue accessibility strongly impacted induced antibody responses. The solvent-exposed MPER tryptophan residue (Trp-680) was immunodominant, focusing immune responses, despite sequence variability elsewhere. Nonetheless, immunogenicity could be readily manipulated using site-directed mutagenesis or structural constraints to modulate amino acid surface display. These studies provide fundamental insights for immunogen design aimed at targeting B cell antibody responses.

Full Text

Duke Authors

Cited Authors

  • Kim, M; Song, L; Moon, J; Sun, Z-YJ; Bershteyn, A; Hanson, M; Cain, D; Goka, S; Kelsoe, G; Wagner, G; Irvine, D; Reinherz, EL

Published Date

  • November 1, 2013

Published In

Volume / Issue

  • 288 / 44

Start / End Page

  • 31888 - 31901

PubMed ID

  • 24047898

Pubmed Central ID

  • PMC3814781

Electronic International Standard Serial Number (EISSN)

  • 1083-351X

Digital Object Identifier (DOI)

  • 10.1074/jbc.M113.494609


  • eng

Conference Location

  • United States