title: Neutralizing human monoclonal antibodies to conformational epitopes of human T-cell lymphotropic virus type 1 and 2 gp46.
abstract: Ten human monoclonal antibodies derived from peripheral B cells of a patient with human T-cell lymphotropic virus (HTLV)-associated myelopathy are described. One monoclonal antibody recognized a linear epitope within the carboxy-terminal 43 amino acids of HTLV gp21, and two monoclonal antibodies recognized linear epitopes within HTLV type 1 (HTLV-1) gp46. The remaining seven monoclonal antibodies recognized denaturation-sensitive epitopes within HTLV-1 gp46 that were expressed on the surfaces of infected cells. Two of these antibodies also bound to viable HTLV-2 infected cells and immunoprecipitated HTLV-2 gp46. Virus neutralization was determined by syncytium inhibition assays. Eight monoclonal antibodies, including all seven that recognized denaturation-sensitive epitopes within HTLV-1 gp46, possessed significant virus neutralization activity. By competitive inhibition analysis it was determined that these antibodies recognized at least four distinct conformational epitopes within HTLV-1 gp46. These findings indicate the importance of conformational epitopes within HTLV-1 gp46 in mediating a neutralizing antibody response to HTLV infection.
authors.affiliation: Department of Pathology, Stanford University School of Medicine, California 94305, USA. k.g.hadlock@forsythe.stanford.edu
authors.forename: K G
authors.initials: KG
authors.lastname: Hadlock
authors.forename: J
authors.initials: J
authors.lastname: Rowe
authors.forename: S
authors.initials: S
authors.lastname: Perkins
authors.forename: P
authors.initials: P
authors.lastname: Bradshaw
authors.forename: G Y
authors.initials: GY
authors.lastname: Song
authors.forename: C
authors.initials: C
authors.lastname: Cheng
authors.forename: J
authors.initials: J
authors.lastname: Yang
authors.forename: R
authors.initials: R
authors.lastname: Gascon
authors.forename: J
authors.initials: J
authors.lastname: Halmos
authors.forename: S M
authors.initials: SM
authors.lastname: Rehman
authors.forename: M S
authors.initials: MS
authors.lastname: McGrath
authors.forename: S K
authors.initials: SK
authors.lastname: Foung
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology*; D015153:Blotting, Western; D002460:Cell Line; D018604:Epitope Mapping; D015686:Gene Products, env / Q000276:immunology*; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D015367:Human T-lymphotropic virus 2 / Q000276:immunology*; D006801:Humans; D009500:Neutralization Tests; D011233:Precipitin Tests; D011487:Protein Conformation; D015682:Retroviridae Proteins, Oncogenic / Q000276:immunology*; D054299:env Gene Products, Human Immunodeficiency Virus
chemical_list: D000911:Antibodies, Monoclonal; D015686:Gene Products, env; D015682:Retroviridae Proteins, Oncogenic; D054299:env Gene Products, Human Immunodeficiency Virus; C055266:gp46 protein, Human T-cell leukemia virus type I; C069568:gp46 protein, Human immunodeficiency virus 2