title: Functional and Molecular Characteristics of Novel and Conserved Cross-Clade HIV Envelope Specific Human Monoclonal Antibodies.
abstract: To define features of the B cell response to HIV that may be translated to vaccine development, we have isolated a panel of monoclonal antibodies (MAbs) from HIV-infected patients. These MAbs are all highly reactive to HIV envelope (Env) from multiple clades, and include gp120 and gp41 specificities. Three of the MAbs exhibit substantial homology to previously described VH1-69, VH3-30, and VH4-59 HIV broadly neutralizing antibody lineages. An inherently autoreactive VH4-34 encoded MAb was reactive to diverse Env despite its minimal mutation from germline. Its isolation is consistent with our previous observation of increased VH4-34+antibodies in HIV-infected patients. These results suggest that conserved developmental processes contribute to immunoglobulin repertoire usage and maturation in response to HIV Env and that intrinsically autoreactive VH genes, despite the absence of mutation, could serve as effective templates for maturation and development of protective antibodies. These results also bear significant implications for the development of immunogens.
authors.affiliation: 1 Division of Infectious Diseases, University of Rochester Medical Center , Rochester, New York.
authors.forename: James J
authors.initials: JJ
authors.lastname: Kobie
authors.forename: Bo
authors.initials: B
authors.lastname: Zheng
authors.forename: Michael S
authors.initials: MS
authors.lastname: Piepenbrink
authors.forename: Ann J
authors.initials: AJ
authors.lastname: Hessell
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Haigwood
authors.forename: Michael C
authors.initials: MC
authors.lastname: Keefer
authors.forename: Ignacio
authors.initials: I
authors.lastname: Sanz
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000494:pharmacology; D057134:Antibodies, Neutralizing / Q000737:chemistry* / Q000494:pharmacology; D000914:Antibodies, Viral / Q000737:chemistry* / Q000494:pharmacology; D005260:Female; D057809:HEK293 Cells; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015700:HIV Envelope Protein gp41 / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011485:Protein Binding
chemical_list: D019380:Anti-HIV Agents; D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D007074:Immunoglobulin G