Development of specific monoclonal antibodies that recognize the cytoplasmic CRGKA conserved domain of all variant-specific surface proteins of Giardia lamblia

ALICIA SAURA; CÉSAR GERMÁN PRUCCA; FERNANDO DAVID RIVERO; HUGO DANIEL LUJAN.

Rosario. Argentina.

Congreso; VIII congreso Argentino de Protozoología y Enfermedades parasitarias. Sociedad Argentina de Protozoología; 2008

Giardia lamblia is an intestinal parasitic organism that undergoes antigenic variation, a mechanism that allows the parasite to evade the host’s immune system. Individual Giardia trophozoites are totally covered by only one member of a family of antigenic distinct proteins called variant-specific surface proteins (VSPs). The spontaneous change of this surface proteins leads to the development of chronic and/or recurrent infections in several vertebrate host, including humans and domestic and farm animals. VSPs are plasma membrane type I integral proteins ranging in size from 20 to 200 KDa. They present a variable N-terminal extracellular region, and a highly conserved carboxyl terminal transmembrane region that includes a 5- amino acid cytoplasmic tail (CRGKA). We have recently demonstrated an RNAi-like mechanism is involved in regulating surface antigen switching in Giardia and that its disruption abolished antigenic variation. In addition, infection of gerbils with trophozoites expressing the entire repertoire of VSP protected the animals against subsequent infections. In this work, we present the development of several monoclonal antibodies (mAb) that recognizes specifically the CRGKA conserved domain of all VSPs. These mAbs specifically recognizes the surface of all the trophozoites, whatever VSP is expressed. This antibody constitutes both a new reagent to study antigenic variation in Giardia and a fundamental tool for the development of a vaccine against this important parasite.