IDENTIFICATION OF IMMUNODOMINANT EPITOPES IN TRYPANOSOMA-CRUZI TRYPOMASTIGOTE SURFACE ANTIGEN-1 PROTEIN THAT MASK PROTECTIVE EPITOPES

The gene that encodes trypomastigote surface Ag-1 (TSA-1), a major sur face Ag of the bloodstream trypomastigote stage of Trypanosoma cruzi, was expressed in a baculovirus expression system. To determine the epi tope(s) in TSA-1 that was recognized during T. cruzi infection and aft er immunization with TSA-1, subregions of the TSA-1 gene were expresse d in a bacterial expression system. As seen by Western blotting, both mice and rabbits immunized with recombinant TSA-1 protein, as well as T. cruzi-infected mice, developed strong immune responses to the carbo xyl-proximal region of TSA-1, but show no reaction to the amino-proxim al portion of TSA-1. When mice were immunized with either recombinant TSA-1 protein or the carboxyl-proximal region of TSA-1, they did not s urvive challenge with 10(3) bloodstream trypomastigotes. However, 70% of the mice immunized with the amino-proximal portion of TSA-1 survive d challenge with 10(3) bloodstream trypomastigotes. Thus, the immune r esponses elicited by recombinant TSA-1 or the carboxyl-proximal portio n of TSA-1 are nonprotective during T. cruzi infection. In contrast, v accination with the amino proximal region of TSA-1 elicits a protectiv e immune response. These results suggest that responses to immunodomin ant epitope(s) within the carboxyl-proximal portion of TSA-1 mask epit opes within the amino-proximal portion that are capable of stimulating host-protective immune responses. It is suggested that immunodominant regions in surface molecules such as TSA-1 may provide a mechanism fo r the parasite to evade the host immune response by directing the resp onse away from epitopes that have the potential to elicit a reaction t hat is damaging to the parasite.