Giardia lamblia variant surface protein H7 stimulates a heterogeneous repertoire of antibodies displaying differential cytological effects on the parasite

Abstract

Previous investigations had shown that the Giardia lamblia clone GS/M-83-H7-specific variant surface protein (VSP) H7 consists of at least two antigenically distinct parts: (i) a variable 314-aa N-terminal region which contains one, or more, variant-specific epitopes eliciting a transient and consequently low-level antibody response preferentially detectable during the early phase of a G. lamblia infection in mice; and (ii) a 171-aa C-terminal region which contains relatively conserved epitope(s) causing a persistent and consequently high-level antibody response during the later phase of an infection. The present study indicated that monoclonal antibody G10/4 and polyclonal antibodies from early-phase infected or hyperimmunized mice, directed against the variant-specific N-terminal region, exclusively recognized conformational cysteine-containing epitopes. These antibodies caused detachment and aggregation of trophozoites, and exhibited complement-independent cytotoxic effect towards the parasite. In contrast, polyclonal antibodies from late-phase infected mice, directed against the semi-conserved peptidyl structures in the C-terminal region, preferentially reacted with non-conformational epitopes. Such antibodies had no cytotoxic effect, but provoked parasite-detachment and -aggregation. These findings indicated that infection of mice with G. lamblia clone GS/M-83-H7 generates a heterogeneous repertoire of cytologically active anti-VSP H7 antibodies which may have a direct influence on the course of the parasite infection.