The surface glycoproteins of Trypanosoma cruzi encode a superfamily of variant T cell epitopes

Trypanosoma cruzi is an obligate intracellular protozoan parasite. During mammalian infection, extracellular and intracellular parasites simultaneously express multiple members of a polymorphic surface protein superfamily. The effect of this extensive surface protein polymorphism on the mammalian host T cell response is not known. In this report, we identified a surface protein MHC class II-restricted T cell epitope (epitope 1), and cloned 10 surface protein cDNAs that encode epitope 1 variants. All these cDNA variant epitopes were processed and presented to T cells, and some functioned as partial T cell agonists. CD4 T cells primed with epitope 1, and challenged with epitope 1, proliferated and expressed IFN-gamma and IL-4. In contrast, CD4 T cells primed with a mixture of variant epitopes and epitope 1, and challenged with epitope 1, expressed IL-4, but did not proliferate or express IFN-gamma. The data suggest that the simultaneous expression of polymorphic surface proteins that encode variant T cell epitopes may limit the expression of each surface protein epitope below a threshold level required to stimulate a protective IFN-gamma response against that epitope. This system of T cell evasion is unique and contrasts with the sequential antigenic variation used by African trypanosomes to evade Abs directed against their surface proteins.