The influence of molecular heterogeneity in helminth identification, protective immunity and immunodiagnosis

Abstract

In almost any area of research into parasitic helminths, molecular heterogeneity is an important factor. The identification of heterogeneous proteins and genes is central to studies of parasite taxonomy and identification. The identification of species and strain specific antigens is a necessary prerequisite of accurate immunodiagnosis. In addition, knowledge of the extent of heterogeneity in key protective antigens is important to understanding protective immunity and evaluating the possibilities of successful vaccination. There is little doubt that each of these areas will rapidly progress during the next few years as they are studied increasingly at the level of gene structure. Using the techniques of gene cloning, mapping and sequencing as well as sensitive hybridisation probes the speed and detail of molecular analysis is increased by at least an order of magnitude as compared with studies of fully processed gene products isolated from the organisms in question. Genes encoding species specific genes can rapidly be identified by screening with nucleotide probes and those which express species specific antigens by screening with antibodies. Similarly if a gene of one species is cloned it can be immediately used to identify the corresponding genes (where they exist) in other species and DN A sequencing can then rapidly assess variation between them. At the time of writing we appear to be in the situation where cDNA and genomic libraries are available for most of the major parasitic helminths but where little data concerning individual genes has yet reached the press or even the “grapevine”. We can thus quite reasonably expect an explosion of knowledge in our understanding of protein and gene heterogeneity and diversity in the coming months and years. A probable outcome of this molecular biological approach is that the boundaries beween the fields will rapidly become blurred. The same gene which encodes a protective antigen may well represent an excellent means of diagnosis and an important probe for phylogenetic relationships! The power of molecular biology will also facilitate progress in the area of molecular heterogeneity in which little progress has yet been made, i.e. linking molecular differences to major behavioural and medically important variations. The gap in knowledge hitherto preventing this was the identity and function of individual molecules. By comparing DNA sequences of cloned genes with the sequences of all previously cloned genes and searching for homologies it is now often possible to identify a likely function for individual polypeptides. Thus all of the studies described here will take on a new level of significance and interest and eventually will lead to a profound understanding of host parasite relationships and parasitism.