Neutralizing Human Monoclonal Antibodies to Conformational

Ten human monoclonal antibodies derived from peripheral B cells of a patient with human T-cell lympho-tropic 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 neu-tralization 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. Human T-cell lymphotropic virus types 1 and 2 (HTLV-1 and HTLV-2) are members of the primate T-cell lymphoma/ leukemia viruses. HTLV-1 causes adult T-cell leukemia (re-viewed in reference 6) and a neurological disorder, HTLV