Antigenic variation is a sophisticated molecular mechanism that allows parasites, viruses, and some bacteria to escape the immune response of the invaded host, by changing the nature of their expressed surface antigens. Classical examples are (a) trypanosomes amongst parasites and (b) influzenza virus.
Trypanosomes are infectious agents transmitted by glossinas and are responsible for severe tropical diseases, such as sleeping sickness in humans. Trypanosomes express surface glycoproteins that induce an immune response in the host. Although at any given time one trypanosome expresses one surface glycoprotein, it may switch to the expression of another one, having a slightly different structure. There are large numbers of these different forms (up to 1000), called variable surface glycoproteins (VSG), each being encoded by a distinct gene. There are two known mechanisms that account for the successive expression of different VSG genes. One is transposition that brings a gene that was present initially as part of one of several gene clusters, scattered on different chromosomes, to one telomere end. As a consequence of the transposition, that gene is expressed, until another one becomes functional. An alternative mechanism is a change in the control of transcription of expression sites. As the structure varies from one VSG to another, there is a permanent change in antigenicity of the parasite population, thereby ensuring escape from the immune mechanisms of the host. Although a large number of genes are potentially active, only a limited fraction is used, so that the repertoire of different VSGs expressed in one host remains limited; this may explain the appearance of chronic immunity in tropical populations.
Viruses use a different mechanism to escape the immune system. One example is that of influenza A, which expresses two surface antigens, hemagglutinin and neuraminidase. It is well known that new variants always arise, sometimes being highly dangerous as they spread rapidly. New variants are the result of mutations, which induce antigenic drift, and exchange of genetic material between different virus strains, leading to antigenic shift, which has a more drastic impact on spreading of the virus. Antigenic variation of viruses is a major drawback in preventing infection (see Virus Infection, Animal). One approach is to prepare modified strains by site-directed mutagenesis and thus produce vaccines that might anticipate their natural variation.
A more recent problem of antigenic variation is that by HIV, which mutates rapidly, leading to the rapid accumulation of numerous variants within the same patient and providing a particularly efficient way for the virus to escape the immune system. Added to the fact that lymphocytes themselves area major target for this virus, this stresses the unusual danger of this virus.
