Isolation of a human anti-HIV gp41 membrane proximal region neutralizing antibody by antigen-specific single B cell sorting |
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Authors: | Morris Lynn Chen Xi Alam Munir Tomaras Georgia Zhang Ruijun Marshall Dawn J Chen Bing Parks Robert Foulger Andrew Jaeger Frederick Donathan Michele Bilska Mira Gray Elin S Abdool Karim Salim S Kepler Thomas B Whitesides John Montefiori David Moody M Anthony Liao Hua-Xin Haynes Barton F |
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Affiliation: | Duke Human Vaccine Institute and Departments of Medicine, Surgery and Immunology, Duke University School of Medicine, Durham, North Carolina, United States of America. lynnm@nicd.ac.za |
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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 (V(H)1-69) and variable kappa light chain (V(K)3-20) 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. |
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