title: Isolation of a human anti-HIV gp41 membrane proximal region neutralizing antibody by antigen-specific single B cell sorting.
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.
authors: 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
authors: Lynn
authors: L
authors: Morris
authors: Xi
authors: X
authors: Chen
authors: Munir
authors: M
authors: Alam
authors: Georgia
authors: G
authors: Tomaras
authors: Ruijun
authors: R
authors: Zhang
authors: Dawn J
authors: DJ
authors: Marshall
authors: Bing
authors: B
authors: Chen
authors: Robert
authors: R
authors: Parks
authors: Andrew
authors: A
authors: Foulger
authors: Frederick
authors: F
authors: Jaeger
authors: Michele
authors: M
authors: Donathan
authors: Mira
authors: M
authors: Bilska
authors: Elin S
authors: ES
authors: Gray
authors: Salim S
authors: SS
authors: Abdool Karim
authors: Thomas B
authors: TB
authors: Kepler
authors: John
authors: J
authors: Whitesides
authors: David
authors: D
authors: Montefiori
authors: M Anthony
authors: MA
authors: Moody
authors: Hua-Xin
authors: HX
authors: Liao
authors: Barton F
authors: BF
authors: Haynes
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry; D057134:Antibodies, Neutralizing / Q000737:chemistry; D002469:Cell Separation; D000939:Epitopes / Q000737:chemistry; D005434:Flow Cytometry / Q000379:methods; D019793:Fluorescein / Q000737:chemistry; D015700:HIV Envelope Protein gp41 / Q000235:genetics*; D015658:HIV Infections / Q000097:blood; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000737:chemistry; D007700:Kinetics; D010455:Peptides / Q000737:chemistry; D017434:Protein Structure, Tertiary; D020349:Surface Plasmon Resonance
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000939:Epitopes; D015700:HIV Envelope Protein gp41; D007135:Immunoglobulin Variable Region; D010455:Peptides; D019793:Fluorescein