4.3 Article

Frequency of specific CD8+T cells for a promiscuous epitope derived from Trypanosoma cruzi KMP-11 protein in chagasic patients

Journal

PARASITE IMMUNOLOGY
Volume 32, Issue 7, Pages 494-502

Publisher

WILEY
DOI: 10.1111/j.1365-3024.2010.01206.x

Keywords

CD8(+) T cell; Chagas' disease; HLA-A2 supertype; Trypanosoma cruzi

Funding

  1. Colciencias Research [1203-333-18692]
  2. PAI (Junta de Andalucia) [P06-CTS-02242]
  3. [RICET-RD06/0021-0014]

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The K1 peptide is a CD8+T cell HLA-A*0201-restricted epitope derived from the Trypanosoma cruzi KMP-11 protein. We have previously shown that this peptide induces IFN-gamma secretion by CD8+T cells. The aim of this study was to characterize the frequency of K1-specific CD8+T cells in chagasic patients. Nineteen HLA-A2+individuals were selected from 50 T. cruzi infected patients using flow cytometry and SSP-PCR assays. Twelve HLA-A*0201+noninfected donors were included as controls. Peripheral blood mononuclear cells were stained with HLA-A2-K1 tetramer, showing that 15 of 19 infected patients have K1-specific CD8+T cells (0 center dot 09-0 center dot 34% frequency) without differences in disease stages or severity. Of note, five of these responders were A*0205, A*0222, A*0226, A*0259 and A*0287 after molecular typing. Thus, a phenotypic and functional comparison of K1-specific CD8+T cells from non-HLA-A*0201 and HLA-A*0201+infected patients was performed. The results showed that both non-HLA-A*0201 and HLA-A*0201+individuals have a predominant effector memory CD8+T cell phenotype (CCR7-, CD62L-). Moreover, CD8+T cells from non-HLA-A*0201 and HLA-A*0201+individuals expressed IL-2, IFN-gamma and perforin without any differences. These findings support that K1 peptide is a promiscuous epitope presented by HLA-A2 supertype molecules and is highly recognized by chagasic patients.

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