Schistosoma mansoni: structural and biophysical aspects of Lewis X-antibody interactions

Abstract

Schistosomiasis (Bilharzia) is a tropical parasitic disease caused by schistosomes. At present more than 200 million people are infected by these parasites. If the infection is left untreated, the parasites can survive within the body for 5 years or more. The parasite has developed r escape mechanisms to escape the immune response of its host. The production by the parasite of heavily glycosylated proteins and lipids is thought to play an important role in this. One important carbohydrate structure expressed in all stages is the trisaccharide Lewis X (Le^x). By measuring the interaction with mono-, di-, and trimeric Lex of antibodies both in vitro and in vivo it has become clear that the humoral immune response to the various oligomeric forms of Le^x is different. This can now be taken into account in further studies in which the humoral and cellular immunogenicity of Le^x is investigated. Next, the elucidation of the crystal structure of a monoclonal antibody in complex with Le^x has led to a better insight in protein-carbohydrage interactions on the molecular level. This new knowledge can be used for further improvement of diagnostic techniques for schistosomiasis, and also for a better understanding of this and other diseases in which Le^x plays a role (e.g. cancer).