CD8+ T-Cell Responses to Trypanosoma cruzi Are Highly Focused on Strain-Variant trans-Sialidase Epitopes

CD8 + T cells are crucial for control of a number of medically important protozoan parasites, including Trypanosoma cruzi, the agent of human Chagas disease . Yet, in contrast to the wealth of information from viral and bacterial infections, little is known about the antigen specificity or the general development of effector and memory T-cell responses in hosts infected with protozoans. In this study we report on a wide-scale screen for the dominant parasite peptides recognized by CD8 + T cells in T. cruzi –infected mice and humans. This analysis demonstrates that in both hosts the CD8 + T-cell response is highly focused on epitopes encoded by members of the large trans -sialidase family of genes. Responses to a restricted set of immunodominant peptides were especially pronounced in T. cruzi –infected mice, with more than 30% of the CD8 + T-cell response at the peak of infection specific for two major groups of trans -sialidase peptides. Experimental models also demonstrated that the dominance patterns vary depending on the infective strain of T. cruzi, suggesting that immune evasion may be occurring at a population rather than single-parasite level.