Abstract

The CD4+ and CD8+ T cell immune response against T. cruzi, the parasite causing Chagas disease, are relevant for both parasite control and disease pathogenesis. Several studies have been focused on their phenotype and functionally, but only a few have drilled down to identify the parasite proteins that are processed and presented to these cells, especially to CD4+ T lymphocytes. Although approximately 10,000 proteins are encoded per haploid T. cruzi genome, fewer than 200 T cell epitopes from 49 T. cruzi proteins have been identified so far. In this context, a detailed knowledge of the specific targets of T cell memory response emerges as a prime tool for the conceptualization and development of prophylactic or therapeutic vaccines, an approach with great potential to prevent and treat this chronic disease. Here, we review the available information about this topic in a comprehensive manner and discuss the future challenges in the field.

Highlights

  • Chagas disease, caused by the infection with the protozoan Trypanosoma cruzi, is a neglected tropical disease from the American continent that has spread from the limits established by vector ecology due to human migration [1] to non-endemic places such Canada, USA, Europe, Australia and Japan [2]

  • A1 and a2 domains ligated to the mouse a3, transmembrane and cytoplasmic H2-Kb domains). Splenocytes from these animals were submitted to cytotoxicity assays, in which Jurkat A2.1/Kb or lymphoblastoid 721.221 A2.1/Kb targets cells were sensitized with trypomastigote surface antigen (TSA)-1, amastigote surface proteins (ASP)-1- and amastigote surface protein-2 (ASP-2)-derived peptides [36]

  • Experimental animal models and studies with clinical samples have shown that CD4+ and CD8+ T cells play a crucial role in the control of Chagas disease

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Summary

INTRODUCTION

Chagas disease, caused by the infection with the protozoan Trypanosoma cruzi, is a neglected tropical disease from the American continent that has spread from the limits established by vector ecology due to human migration [1] to non-endemic places such Canada, USA, Europe, Australia and Japan [2]. If patients are not treated, a chronic phase follows, during which most people remain asymptomatic but infected for life. It is estimated that up to 40% of chronically infected patients can develop organ involvement, being cardiomyopathy and megaviscera (megaoesophagus, megacolon, or both) the most prevailing [5]. Based on these phases, some diagnostic tests are better suited than others. With regard to Chagas disease treatment, two drugs -benznidazole and nifurtimox- are currently available. Despite their effectiveness in the acute phase, there is no consensus for their use in the chronic phase. In patients with digestive involvement, conservative or even surgical treatment is indicated depending on the stage of the disease [2]

SPECIFIC T CELL RESPONSE IN CHAGAS DISEASE
MODELS FOR CHAGAS DISEASE SPECIFIC T CELL RESPONSE
VLAKDGTEV IAGGVMAVV FVNHDFTVV LLLLGLWGL LLGLWGLTGL WVFPESISPV FVNHRFTLV
TLLTIDGGI TLQPVERVL
TVPYHFANSKFTLVA MLSLVAAVKAPRTHN GVVMEDGTLVFPLMA HRFTLVATVTIHQVPK
EMHC Reference Restriction
CHAGAS DISEASE
CONCLUDING REMARKS AND FUTURE PERSPECTIVES
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