Identification of new epitopes recognized by human monoclonal antibodies with neutralizing and antibody-dependent cellular cytotoxicity activities specific for human T cell leukemia virus type 1.
We have generated a number of EBV-transformed B cell lines producing human mAb against human T cell leukemia virus type 1 (HTLV-1) from the peripheral blood B lymphocytes obtained from patients with HTLV-1-associated myelopathy/tropical spastic paraparesis. Various synthetic peptides corresponding to antigenic regions of HTLV-1 gag and env proteins were used for the screening of antibodies in ELISA. In our study, four IgG mAb to the gag p19 amino acids 100 to 130, and 5 IgG mAb to the env p46 amino acids 175 to 199 were characterized. An immunofluorescence assay showed that all of these mAb specifically bound to the surface of HTLV-1-bearing cell lines. Among these mAb, one anti-gp46 mAb, designated KE36-11, neutralized the infectivity of HTLV-1 as determined by both the inhibition of HTLV-1-induced syncytium formation and transformation assays in vitro. An antibody-binding assay using overlapping oligopeptides revealed that KE36-11 recognized a new epitope locating between the gp46 amino acid sequence 187-193 (Ala-Pro-Pro-Leu-Leu-Pro-His). Another anti-gp46 mAb, designated KE36-7, showed antibody-dependent cellular cytotoxicity against HTLV-1-bearing cell line. KE36-7 bound strongly to the 10-mer peptide-gp46 187-196, and weakly to peptides containing the gp46 amino acid sequence 191-196 (Leu-Pro-His-Ser-Asn-Leu). These two epitopes, which are associated with HTLV-1 neutralization and antibody-dependent cellular cytotoxicity, are thus the first epitopes identified in human HTLV-1 infection. It is possible that passive immunization of humans with these two human mAb are effective on the protection of HTLV-1 infection in vivo.
Kuroki
M
M
First Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Nakamura
M
M
Itoyama
Y
Y
Tanaka
Y
Y
Shiraki
H
H
Baba
E
E
Esaki
T
T
Tatsumoto
T
T
Nagafuchi
S
S
Nakano
S
S
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000920:Antibody-Dependent Cell Cytotoxicity; D002472:Cell Transformation, Viral; D015480:Deltaretrovirus Antibodies / Q000276:immunology*; D015485:Deltaretrovirus Antigens / Q000276:immunology*; D000939:Epitopes; D015686:Gene Products, env / Q000276:immunology; D015683:Gene Products, gag / Q000276:immunology; D004854:Herpesvirus 4, Human; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010455:Peptides / Q000737:chemistry / Q000276:immunology
D000911:Antibodies, Monoclonal; D015480:Deltaretrovirus Antibodies; D015485:Deltaretrovirus Antigens; D000939:Epitopes; D015686:Gene Products, env; D015683:Gene Products, gag; D010455:Peptides