Neutralizing human monoclonal antibodies to conformational epitopes of human T-cell lymphotropic virus type 1 and 2 gp46.
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.
Hadlock
K G
KG
Department of Pathology, Stanford University School of Medicine, California 94305, USA. k.g.hadlock@forsythe.stanford.edu
Rowe
J
J
Perkins
S
S
Bradshaw
P
P
Song
G Y
GY
Cheng
C
C
Yang
J
J
Gascon
R
R
Halmos
J
J
Rehman
S M
SM
McGrath
M S
MS
Foung
S K
SK
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
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