title: HIV-1 V3 loop crown epitope-focused mimotope selection by patient serum from random phage display libraries: implications for the epitope structural features.
abstract: The crown region of the V3 loop in HIV-1 that contains the conserved amino acid sequence GPGR/G is known as the principal neutralizing determinant due to the extraordinary ability of antibodies to this region to neutralize the virus. To complement the existing peptide models of this epitope, we describe a family of 18 phage-displayed peptides, which include linear 12mer and constrained 7mer peptides that was selected by screening random libraries with serum from HIV-1 subtype B-infected patients. The 7mer constrained peptides presented two conserved amino acid sequences: PR-L in N-terminus and GPG in the C-terminus. On the basis of these peptides we propose a mimotope model of the V3 crown epitope in which the PR-L and GPG sequences represent the two known epitope binding sites. The GPG, has the same function as the V3 crown GPGR sequence but without the involvement of the "R" despite its being considered as the signature of the epitope in B-subtype viruses. The PR-L contains a proline not existing in the epitope that is postulated to induce kinks in the backbones of all peptides and create a spatial element mimicking the N-terminal conformationally variable binding site. Rabbit serum to these mimotopes recognized the V3 peptides and moderately decreased the fusion between HIV-1 Env- and CD4-expressing Jurkat cells. This study proposes the efficient generation by means of patient sera of V3 epitope mimics validated by interaction with the antibodies to contemporary viruses induced in patients. The serum antibody-selectable mimotopes are sources of novel information on the fine structure-function properties of HIV-1 principal neutralizing domain and candidate anti-HIV-1 immunogens.
authors.affiliation: Department of Medicine Genomics and Environmental Toxicology, Institute of the Biomedical Research, Mexican National University, Ciudad Universitaria, 3er Circuito Exterior S/N, Mexico-City 04510, Mexico. karlen@unam.mx
authors.forename: Karlen G
authors.initials: KG
authors.lastname: Gazarian
authors.forename: Yadira
authors.initials: Y
authors.lastname: Palacios-Rodríguez
authors.forename: Tatiana G
authors.initials: TG
authors.lastname: Gazarian
authors.forename: Leonor
authors.initials: L
authors.lastname: Huerta
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D061505:Cell Surface Display Techniques; D018604:Epitope Mapping; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D015483:HIV Antibodies / Q000097:blood / Q000276:immunology / Q000302:isolation & purification; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology / Q000302:isolation & purification; D008561:Membrane Fusion / Q000276:immunology; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology*; D019151:Peptide Library; D011817:Rabbits
chemical_list: D000939:Epitopes; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D007074:Immunoglobulin G; D010446:Peptide Fragments; D019151:Peptide Library