Antigenic variation in protozoan parasites is considered a spontaneous process and antibodies to these variant antigens were cytotoxic. The clearance of the former antigen during antigenic switching is thought to occur by dilution of the original antigen. In this work, the authors provide in vitro and in vivo evidence, that low concentrations of antibodies against Variant-specific Surface Proteins (VSPs) of the intestinal parasite Giardia lamblia are not cytotoxic but induce a robust stimulation of the switching process and the release of the former antigen into extracellular microvesicles. This process is mediated by antibody-induced clustering of VSPs into Lo-phase membrane microdomains through the raftophilic capability of the highly conserved transmembrane domain of the VSPs.
- Albano H. Tenaglia
- Lucas A. Luján
- Hugo D. Luján