Abstract
BackgroundPreviously, we identified a set of HLA-A020.1-restricted trans-sialidase peptides as targets of CD8+ T cell responses in HLA-A0201+ individuals chronically infected by T. cruzi.Methods and FindingsHerein, we report the identification of peptides encoded by the same trans-sialidase gene family that bind alleles representative of the 6 most common class I HLA-supertypes. Based on a combination of bioinformatic predictions and HLA-supertype considerations, a total of 1001 epitopes predicted to bind to HLA A01, A02, A03, A24, B7 and B44 supertypes was selected. Ninety-six supertype-binder epitopes encoded by multiple trans-sialidase genes were tested for the ability to stimulate a recall CD8+ T cell response in the peripheral blood from subjects with chronic T. cruzi infection regardless the HLA haplotype. An overall hierarchy of antigenicity was apparent, with the A02 supertype peptides being the most frequently recognized in the Chagas disease population followed by the A03 and the A24 supertype epitopes. CD8+ T cell responses to promiscuous epitopes revealed that the CD8+ T cell compartment specific for T. cruzi displays a functional profile with T cells secreting interferon-γ alone as the predominant pattern and very low prevalence of single IL-2-secreting or dual IFN-γ/IL-2 secreting T cells denoting a lack of polyfunctional cytokine responses in chronic T. cruzi infection.ConclusionsThis study identifies a set of T. cruzi peptides that should prove useful for monitoring immune competence and changes in infection and disease status in individuals with chronic Chagas disease.
Highlights
Trypanosoma cruzi, the causative agent of Chagas disease, constitutes a prominent human health problem in Central and South America [1]
This study identifies a set of T. cruzi peptides that should prove useful for monitoring immune competence and changes in infection and disease status in individuals with chronic Chagas disease
Supporting the hypothesis that disease is less severe when immune control is more efficient we have shown that chronic chagasic subjects with no or mild clinical disease have significantly higher frequency of interferon-gamma (IFN-c) producing T cells specific for T. cruzi than do individuals with more severe disease [7,8]
Summary
Trypanosoma cruzi, the causative agent of Chagas disease, constitutes a prominent human health problem in Central and South America [1]. Supporting the hypothesis that disease is less severe when immune control is more efficient we have shown that chronic chagasic subjects with no or mild clinical disease have significantly higher frequency of interferon-gamma (IFN-c) producing T cells specific for T. cruzi than do individuals with more severe disease [7,8]. This apparent impairment in CD8+ T cell responses was associated with an increased frequency of fully differentiated memory (CD272CD282CD45RA2) CD8+ T cells and a high rate of apoptosis, possibly reflecting exhaustion in the CD8+ T cell compartment [8]. We identified a set of HLA-A020.1-restricted trans-sialidase peptides as targets of CD8+ T cell responses in HLA-A0201+ individuals chronically infected by T. cruzi
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