Authors

N Papavasiliou¹;  ¹ German Cancer Research Center, Germany

Discussion

The African trypanosome survives the immune response of its mammalian host by antigenic variation of its major surface antigen (the Variant Surface Glycoprotein, or VSG). Whilst the genome encodes around 400 complete variants, the genomic archive contains several thousand variant gene fragments that can serve as donor sequences for gene conversion, making the potential number of possible variants very high.
The host response to trypanosomes is chiefly antibody based, and antibodies are also capable of extreme diversification through recombination (Ig gene rearrangments). And yet, this very diverse host response is routinely evaded by trypanosomes.
In recent work we have found that antibody repertoires against specific VSGs are highly restricted, and are directed predominantly to distinct epitopes on the surface of the VSGs. They are also highly discriminatory: minor alterations within these exposed epitopes confer antigenically-distinct properties to these VSGs and elicit different repertoires. We propose that the patterned and repetitive nature of the VSG coat focuses host immunity to a restricted set of immunodominant epitopes per VSG, eliciting a highly stereotyped response, minimizing cross reactivity between different VSGs and facilitating prolonged immune evasion.
Therefore, trypanomes evade the antibody response not only at the macro scale (though antigenic variation and replacement of entire VSG genes) but also at the micro scale (through the establishment of focused immunodominant epitopes that, when replaced, can fuel immune evasion).