Format

Send to

Choose Destination
See comment in PubMed Commons below
J Biol Chem. 2013 Nov 1;288(44):31888-901. doi: 10.1074/jbc.M113.494609. Epub 2013 Sep 18.

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

Author information

1
From the Laboratory of Immunobiology and Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115.

Abstract

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.

KEYWORDS:

Antibodies; HIV-1; Immunodominance; Immunogenicity; Infectious Diseases; Protein Structure; Vaccine Development

PMID:
24047898
PMCID:
PMC3814781
DOI:
10.1074/jbc.M113.494609
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center