Antigenic variation is a strategy by which pathogens alter the proteins or carbohydrates on their surface to evade recognition by the host immune system. By switching between different antigenic forms, organisms can persist in a host despite adaptive immune responses targeting previous variants.
Mechanisms and molecular basis
Antigenic variation encompasses several molecular strategies for changing expressed antigens. In some bacteria, such as Neisseria gonorrhoeae and Borrelia hermsii, gene conversion and homologous recombination replace expressed surface protein genes with silent variants from a repertoire of cassettes, generating new pilin or variable major protein sequences. Phase variation involves reversible on/off switching of gene expression through slipped‑strand mispairing or promoter inversions, altering the presence of pili, flagella or outer membrane proteins. Protozoan parasites like Trypanosoma brucei and Plasmodium falciparum employ large families of variant surface glycoprotein (VSG) or var genes; only one is expressed at a time, and periodic switching allows these parasites to stay ahead of host antibody responses. Viruses can use hypermutation or recombination to diversify surface epitopes; HIV exhibits extensive envelope glycoprotein variability due to rapid mutation and glycan shielding. The common theme is generation of antigenic diversity beyond that produced by point mutation alone, enabling repeated cycles of immune evasion.
Examples and consequences
Antigenic variation underlies chronic and relapsing infections. African trypanosomes sequentially express hundreds of VSG genes, causing waves of parasitaemia as each variant is cleared and replaced by a new one. Relapsing fever spirochetes change their variable major proteins to reappear after apparent clearance. Malaria parasites use var gene switching to adhere to different host receptors and avoid clearance by antibodies, contributing to severe disease and complicating vaccine design. In bacteria, phase variation of capsule or O‑antigen expression allows pathogens like Haemophilus influenzae or Salmonella enterica to evade opsonization and complement. The phenomenon also affects diagnostic assays and epidemiological typing, as antigenic profiles can change within a single lineage. Understanding antigenic variation informs the development of vaccines and therapeutics that target conserved regions or exploit invariant functions.
By rapidly changing surface molecules through gene conversion, phase variation or other mechanisms, pathogens practicing antigenic variation stay one step ahead of host immunity. This dynamic strategy poses challenges for vaccine development and disease control.
Related Terms: Immune evasion, Phase variation, Gene conversion, Variant surface glycoprotein, Plasmodium falciparum