title: epitopes immediately below the base of the V3 loop of gp120 as targets for the initial autologous neutralizing antibody response in two HIV-1 subtype B-infected individuals.
abstract: Epitopes that drive the initial autologous neutralizing antibody response in HIV-1-infected individuals could provide insights for vaccine design. Although highly strain specific, these epitopes are immunogenic, vulnerable to antibody attack on infectious virus, and could be involved in the ontogeny of broadly neutralizing antibody responses. To delineate such epitopes, we used site-directed mutagenesis, autologous plasma samples, and autologous monoclonal antibodies to map the amino acid changes that led to escape from the initial autologous neutralizing antibody response in two HIV-1 subtype B-infected individuals. Additional mapping of the epitopes was accomplished by using alanine scanning mutagenesis. Escape in the two individuals occurred by different pathways, but the responses in both cases appeared to be directed against the same region of gp120. In total, three amino acid positions were identified that were independently associated with autologous neutralization. Positions 295 and 332 are located immediately before and after the N- and C-terminal cysteines of the V3 loop, respectively, the latter of which affected an N-linked glycan that was critical to the neutralization epitope. Position 415 affected an N-linked glycan at position 413 in the C terminus of V4 that might mask epitopes near the base of V3. All three sites lie in close proximity on a four-stranded antiparallel sheet on the outer domain of gp120. We conclude that a region just below the base of the V3 loop, near the coreceptor binding domain of gp120, can be a target for autologous neutralization.
authors: Department of Surgery, Box 2926, Duke University Medical Center, Durham, NC 27710, USA.
authors: Haili
authors: H
authors: Tang
authors: James E
authors: JE
authors: Robinson
authors: S
authors: S
authors: Gnanakaran
authors: Ming
authors: M
authors: Li
authors: Eric S
authors: ES
authors: Rosenberg
authors: Lautaro G
authors: LG
authors: Perez
authors: Barton F
authors: BF
authors: Haynes
authors: Hua-Xin
authors: HX
authors: Liao
authors: Celia C
authors: CC
authors: Labranche
authors: Bette T
authors: BT
authors: Korber
authors: David C
authors: DC
authors: Montefiori
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology*; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D015483:HIV Antibodies / Q000097:blood / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D050505:Mutant Proteins / Q000235:genetics / Q000276:immunology; D009500:Neutralization Tests; D011487:Protein Conformation
chemical_list: D057134:Antibodies, Neutralizing; D000939:Epitopes; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D050505:Mutant Proteins; C514793:gp120 protein, Human immunodeficiency virus 1