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

Publication ,  Journal Article
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 in: J Biol Chem
November 1, 2013

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.

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Published In

J Biol Chem

DOI

EISSN

1083-351X

Publication Date

November 1, 2013

Volume

288

Issue

44

Start / End Page

31888 / 31901

Location

United States

Related Subject Headings

  • Peptides
  • Mutagenesis, Site-Directed
  • Mice, Inbred BALB C
  • Mice
  • Humans
  • HIV-1
  • HIV Envelope Protein gp41
  • Epitopes, B-Lymphocyte
  • Biochemistry & Molecular Biology
  • B-Lymphocytes
 

Citation

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Kim, M., Song, L., Moon, J., Sun, Z.-Y., Bershteyn, A., Hanson, M., … Reinherz, E. L. (2013). Immunogenicity of membrane-bound HIV-1 gp41 membrane-proximal external region (MPER) segments is dominated by residue accessibility and modulated by stereochemistry. J Biol Chem, 288(44), 31888–31901. https://doi.org/10.1074/jbc.M113.494609
Kim, Mikyung, Likai Song, James Moon, Zhen-Yu J. Sun, Anna Bershteyn, Melissa Hanson, Derek Cain, et al. “Immunogenicity of membrane-bound HIV-1 gp41 membrane-proximal external region (MPER) segments is dominated by residue accessibility and modulated by stereochemistry.J Biol Chem 288, no. 44 (November 1, 2013): 31888–901. https://doi.org/10.1074/jbc.M113.494609.
Kim, Mikyung, et al. “Immunogenicity of membrane-bound HIV-1 gp41 membrane-proximal external region (MPER) segments is dominated by residue accessibility and modulated by stereochemistry.J Biol Chem, vol. 288, no. 44, Nov. 2013, pp. 31888–901. Pubmed, doi:10.1074/jbc.M113.494609.
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. Immunogenicity of membrane-bound HIV-1 gp41 membrane-proximal external region (MPER) segments is dominated by residue accessibility and modulated by stereochemistry. J Biol Chem. 2013 Nov 1;288(44):31888–31901.

Published In

J Biol Chem

DOI

EISSN

1083-351X

Publication Date

November 1, 2013

Volume

288

Issue

44

Start / End Page

31888 / 31901

Location

United States

Related Subject Headings

  • Peptides
  • Mutagenesis, Site-Directed
  • Mice, Inbred BALB C
  • Mice
  • Humans
  • HIV-1
  • HIV Envelope Protein gp41
  • Epitopes, B-Lymphocyte
  • Biochemistry & Molecular Biology
  • B-Lymphocytes