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Isolation of a Human Anti-HIV gp41 Membrane Proximal Region Neutralizing Antibody by Antigen-Specific Single B Cell Sorting

Lynn Morris; Xi Chen; Munir Alam; Georgia D. Tomaras; Ruijun Zhang; Dawn J. Marshall; Bing Chen; Robert Parks; Andrew Foulger; Frederick Jaeger; Michele Donathan; Mira Bilska; Elin S. Gray; Salim Abdool Karim; Thomas B. Kepler; John Whitesides; David Montefiori; M. Anthony Moody; Hua-Xin Liao; Barton F. Haynes

Title:
Isolation of a Human Anti-HIV gp41 Membrane Proximal Region Neutralizing Antibody by Antigen-Specific Single B Cell Sorting
Author(s):
Morris, Lynn
Chen, Xi
Alam, Munir
Tomaras, Georgia D.
Zhang, Ruijun
Marshall, Dawn J.
Chen, Bing
Parks, Robert
Foulger, Andrew
Jaeger, Frederick
Donathan, Michele
Bilska, Mira
Gray, Elin S.
Abdool Karim, Salim
Kepler, Thomas B.
Whitesides, John
Montefiori, David
Moody, M. Anthony
Liao, Hua-Xin
Haynes, Barton F.
Date:
Type:
Articles
Department:
Epidemiology
Volume:
6
Permanent URL:
Book/Journal Title:
PLoS ONE
Abstract:
Broadly neutralizing antibodies are not commonly produced in HIV-1 infected individuals nor by experimental HIV-1 vaccines. When these antibodies do occur, it is important to be able to isolate and characterize them to provide clues for vaccine design. CAP206 is a South African subtype C HIV-1-infected individual previously shown to have broadly neutralizing plasma antibodies targeting the envelope gp41 distal membrane proximal external region (MPER). We have now used a fluoresceinated peptide tetramer antigen with specific cell sorting to isolate a human neutralizing monoclonal antibody (mAb) against the HIV-1 envelope gp41 MPER. The isolated recombinant mAb, CAP206-CH12, utilized a portion of the distal MPER (HXB2 amino acid residues, 673–680) and neutralized a subset of HIV-1 pseudoviruses sensitive to CAP206 plasma antibodies. Interestingly, this mAb was polyreactive and used the same germ-line variable heavy (VH1-69) and variable kappa light chain (VK3-20) gene families as the prototype broadly neutralizing anti-MPER mAb, 4E10 (residues 672–680). These data indicate that there are multiple immunogenic targets in the C-terminus of the MPER of HIV-1 gp41 envelope and suggests that gp41 neutralizing epitopes may interact with a restricted set of naive B cells during HIV-1 infection.
Subject(s):
Virology
Immunology
Publisher DOI:
10.1371/journal.pone.0023532
Item views:
269
Metadata:
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