The humoral immune response to human T-cell lymphotropic virus type 1 envelope glycoprotein gp46 is directed primarily against conformational epitopes

Individuals infected with human T-cell lymphotropic virus type 1 (HTLV-1) d evelop a robust immune response to the surface envelope glycoprotein gp46 t hat is partially protective. The relative contribution of antibodies to con formation-dependent epitopes, including those mediating virus neutralizatio n as part of the humoral immune response, is not well defined. We assess in this report the relationship between defined linear and conformational epi topes and the antibodies elicited to these domains. First, five monoclonal antibodies to linear epitopes within gp46 were evaluated for their ability to abrogate binding of three human monoclonal antibodies that inhibit HTLV- l-mediated syncytia formation and recognize conformational epitopes. Bindin g of antibodies to conformational epitopes was unaffected by antibodies to linear epitopes throughout the carboxy-terminal half and central domain of HTLV-1 gp46. Second, an enzyme-linked immunoadsorbent assay was developed a nd used to measure serum antibodies to native and denatured gp46 from HTLV- 1-infected individuals. In sera from infected individuals, reactivity to de natured gp46 had an average of 15% of the reactivity observed to native gp4 6. Third, serum antibodies from 24 of 25 of HTLV-1-infected individuals inh ibited binding of a neutralizing human monoclonal antibody, PRH-7A, to a co nformational epitope on gp46 that is common to HTLV-1 and -2. Thus, antibod ies to conformational epitopes comprise the majority of the immune response to HTLV-1 gp46, and the epitopes recognized by these antibodies do not app ear to involve sequences in previously described immunodominant linear epit opes.