Antigenic variation in clones of Trypanosoma brucei grown in immune-deficient mice

Abstract

We have produced monoclonal antibodies against six variant surface glycoproteins from early variant antigen types (VATs) of the IsTaR 1 serodeme of Trypanosoma brucei brucei. We have used these in fixed cell immunofluorescence assays to follow the VAT composition of populations of each early VAT when passaged through irradiated mice. The IsTat 1.A and 1.7a populations were stable for more than 30 days (approximately 150 generations), but 1.1a, 1.3a, 1.5a, and 1.11a all changed to 1.A within this time. The time and rate of this antigenic switch were characteristic for each VAT. Growth rates of the VATs were determined when they were both grown separately and grown with 1.A. It appeared that the order of growth rates was 1.7a greater than 1.A = 1.1a greater than 1.11a greater than 1.5a greater than 1.3a. We have generated theoretical curves for the replacement of one VAT by another based on differences in their growth rates and the rate at which one VAT switches to another (switch frequency). These curves closely match those derived experimentally. We postulate that the differences in growth rates between VATs and the different switch frequencies for VATs may be sufficient to generate the loosely defined sequence of VATs seen in chronic infections.