African sleeping sickness remains a serious health concern in parts of sub-Saharan Africa, but the implications of this discovery go far beyond Trypanosoma brucei. Many pathogens—including malaria parasites, Plasmodium, and even certain bacteria and viruses—use antigenic variation to evade immune detection.
A new study has shed light on how certain pathogens manage to stay one step ahead of the immune system. By carefully orchestrating changes to their outer surface, parasites like Trypanosoma brucei—the cause of African sleeping sickness—can effectively dodge immune attacks, making infections persistent and difficult to treat. The findings reveal not only how these surface changes happen but also point to new potential strategies for tackling these elusive pathogens.
For the immune system to recognize and neutralize a pathogen, it produces antibodies that latch onto specific molecules—called antigens—on the invader’s surface. But many pathogens, including Trypanosoma brucei, are masters of disguise. They continually change these surface antigens in a process called antigenic variation, preventing existing antibodies from recognizing them.
Until now, scientists didn’t fully understand how these parasites decide which antigen to display next. This new research not only decodes that process but also shows that it’s far from random—it’s tightly controlled by genetic mechanisms.
The team focused their efforts on Trypanosoma brucei, a single-celled parasite transmitted by tsetse flies. The parasite cloaks itself in a dense layer of surface glycoproteins, and it regularly swaps out these molecules to stay hidden.
Their experiments revealed that the trigger for an antigen swap is often a double-strand break in the parasite’s DNA, specifically in the gene coding for the currently active antigen. What happens next depends on the parasite’s genetic toolbox:
- If a homologous repair template is available, the parasite uses segmental gene conversion to repair the break, splicing together bits of different genes to create a mosaic antigen—a completely new disguise for the immune system to contend with.
- If there’s no matching repair template, the parasite activates a different antigen-coding gene located near the telomeres (the ends of chromosomes) from elsewhere in its genome.
By unlocking the secrets of antigenic variation, this research opens exciting new possibilities for fighting infectious diseases that have long outsmarted the immune system.
Journal article: Keneskhanova, Z., et al. 2025. Genomic determinants of antigen expression hierarchy in African trypanosomes. Nature.
Summary by Stefan Botha
