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- W100012129 abstract "Aim Mycobacterium tuberculosis (Mtb) remains a world health threat, with 8.8 million cases reported in 2010, 65% of which were new and recurrent cases of tuberculosis. HLA mediated cellular immune responses are critical for controlling Mtb and recent studies have identified CD8+ T cells as important in controlling infection. Little is known about the minimal Mtb peptide ligands presented during an infection. The objective of this study is to biochemically purify ligands from the HLA of cells infected by Mtb to identify ligands distinct to infected cells. Methods 20 mg of soluble HLA-A ∗ 02:01 were harvested from Mtb infected THP-1 monocyte cells. Peptides were eluted from A ∗ 02:01, fractionated by HPLC, and comparatively analyzed using mass spectrometry (MS). Peptides unique to Mtb infected cells were identified, sequenced by tandem MS, and tested for immunogenicity in an IFNγ ELISOPT assay using PBMC from patients with acute and latent Mtb. Results Five novel Mtb derived ligands from five different Mtb open reading frames were presented by HLA-A ∗ 02:01 during infection. Patient T cells responded to four of the peptides. One peptide, LIL9 from a hypothetical Mtb protein, was dominant relative to the other four peptides, greater in both immunogenicity and in the number of Mtb patients with a response. A ligand from arsA, IMI10, only showed a measurable CD8 T-cell response in patients with latent tuberculosis infection. Conclusions We report the identification and characterization of 5 novel Mtb derived ligands, 4 of which were identified as CD8 T-cell epitopes. We further identify an epitope, who’s specific T-cells are only detectable in patients with latent tuberculosis infection. The reactive Mtb ligands identified not only represent novel epitopes, but also give us a glimpse of what Mtb proteins are processed and presented by class I HLA." @default.
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- W100012129 date "2012-10-01" @default.
- W100012129 modified "2023-09-27" @default.
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- W100012129 doi "https://doi.org/10.1016/j.humimm.2012.07.140" @default.
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