Background: Tuberculosis (TB) is an enduring health problem worldwide and the emerging threat of multidrug\r\nresistant (MDR) TB and extensively drug resistant (XDR) TB is of particular concern. A better understanding of\r\nbiomarkers associated with TB will aid to guide the development of better targets for TB diagnosis and for the\r\ndevelopment of improved TB vaccines.\r\nMethods: Recombinant proteins (n = 7) and peptide pools (n = 14) from M. tuberculosis (M.tb) antigens associated\r\nwith M.tb pathogenicity, modification of cell lipids or cellular metabolism, were used to compare T cell immune\r\nresponses defined by IFN-g production using a whole blood assay (WBA) from i) patients with TB, ii) individuals\r\nrecovered from TB and iii) individuals exposed to TB without evidence of clinical TB infection from Minsk, Belarus.\r\nResults: We identified differences in M.tb target peptide recognition between the test groups, i.e. a frequent\r\nrecognition of antigens associated with lipid metabolism, e.g. cyclopropane fatty acyl phospholipid synthase. The\r\npattern of peptide recognition was broader in blood from healthy individuals and those recovered from TB as\r\ncompared to individuals suffering from pulmonary TB. Detection of biologically relevant M.tb targets was confirmed\r\nby staining for intracellular cytokines (IL-2, TNF-a and IFN-g) in T cells from non-human primates (NHPs) after BCG\r\nvaccination.\r\nConclusions: PBMCs from healthy individuals and those recovered from TB recognized a broader spectrum of M.tb\r\nantigens as compared to patients with TB. The nature of the pattern recognition of a broad panel of M.tb antigens\r\nwill devise better strategies to identify improved diagnostics gauging previous exposure to M.tb; it may also guide\r\nthe development of improved TB-vaccines.
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