Human monoclonal antibody directed against an envelope glycoprotein of human T-cell leukemia virus type I.

Abstract

We report the production and characterization of a human monoclonal antibody reactive against the major envelope glycoprotein of human T-cell leukemia virus type I (HTLV-I), a virus linked to the etiology of adult T-cell leukemia. We exposed lymph-node cells derived from a patient with adult T-cell leukemia to the Epstein-Barr virus in vitro and obtained a B-cell clone (designated 0.5 .alpha.) by a limiting dilution technique. The secreted product of 0.5 .alpha. is a monoclonal antibody (also designated 0.5 .alpha.; that is IgG1 and has K light chains) that binds to the cell membrane of T-cells infected with HTLV-I and lyses them in the presence of complement. The antibody does not react with HTLV-I negative T cells. In electroblot assays, the monoclonal antibody detects a 46-kDa glycoprotein in disrupted HTLV-I virions and a 34-kDa product following digestion of the viral protein with endoglycosidase F. These molecules have been reported to represent the HTLV-I env gene products. The antibody does not react with HTLV-II and HTLV-III virions. Glycoproteins of 61 and 68 kDa, which are known to be encoded at least in part by the env gene of HTLV-I, are precipitated by the antibody from endogenously radiolabeled HTLV-I-infected HUT 102-B2 and MT-2 cells, respectively. These results suggest that this human monoclonal antibody reacts with an env-encoded glycoprotein of HTLV-I. By using a competition assay with a biotin-labeled 0.5.alpha. antibody, we observed that 15 out of 15 patients with adult T-cell leukemia had antibodies that block binding of the 0.5.alpha. antibody to HTLV-I virions. This suggests that the antigen detected by 0.5.alpha. antibody is a common epitope recognized in HTLV-I-infected individuals in vivo. This antibody, as well as the general strategy for making human monoclonal antibodies reactive against pathogenic retroviruses, may have diagnostic or therapeutic application.