03059nas a2200529   4500000000100000008004100001260001300042653002300055653001100078653002600089653001400115653002000129653002700149653001300176653001100189653002500200653001000225653002200235653002500257653001400282100001400296700001200310700002300322700001300345700001400358700001100372700001400383700001300397700001500410700001700425700001400442700001200456700001400468700001200482700001300494700001600507700001500523700001600538700001200554245012600566856004800692300001100740490001600751050001700767520173100784022001402515       2012                            d  c2012 Dec10aBacterial Proteins10aBrazil10aComputational Biology10aCytokines10aEpitope Mapping10aEpitopes, T-Lymphocyte10aEthiopia10aHumans10aMycobacterium leprae10aNepal10aPeptide Fragments10aRecombinant Proteins10aVirulence1 aBobosha K1 aTang ST1 aPloeg-van Schip JJ1 aBekele Y1 aMartins M1 aLund O1 aFranken K1 aKhadge S1 aPontes MAA1 aGonçalves H1 aHussien J1 aThapa P1 aKunwar CB1 aHagge D1 aAseffa A1 aPessolani M1 aPereira GM1 aOttenhoff T1 aGeluk A00aMycobacterium leprae virulence-associated peptides are indicators of exposure to M. leprae in Brazil, Ethiopia and Nepal.  uhttp://www.scielo.br/pdf/mioc/v107s1/18.pdf  a112-230 v107 Suppl 1  aBOBOSHA 20123 a<p>Silent transmission of Mycobacterium leprae, as evidenced by stable leprosy incidence rates in various countries, remains a health challenge despite the implementation of multidrug therapy worldwide. Therefore, the development of tools for the early diagnosis of M. leprae infection should be emphasised in leprosy research. As part of the continuing effort to identify antigens that have diagnostic potential, unique M. leprae peptides derived from predicted virulence-associated proteins (group IV.A) were identified using advanced genome pattern programs and bioinformatics. Based on human leukocyte antigen (HLA)-binding motifs, we selected 21 peptides that were predicted to be promiscuous HLA-class I T-cell epitopes and eight peptides that were predicted to be HLA-class II restricted T-cell epitopes for field-testing in Brazil, Ethiopia and Nepal. High levels of interferon (IFN)-γ were induced when peripheral blood mononuclear cells (PBMCs) from tuberculoid/borderline tuberculoid leprosy patients located in Brazil and Ethiopia were stimulated with the ML2055 p35 peptide. PBMCs that were isolated from healthy endemic controls living in areas with high leprosy prevalence (EChigh) in Ethiopia also responded to the ML2055 p35 peptide. The Brazilian EChigh group recognised the ML1358 p20 and ML1358 p24 peptides. None of the peptides were recognised by PBMCs from healthy controls living in non-endemic region. In Nepal, mixtures of these peptides induced the production of IFN-γ by the PBMCs of leprosy patients and EChigh. Therefore, the M. leprae virulence-associated peptides identified in this study may be useful for identifying exposure to M. leprae in population with differing HLA polymorphisms.</p>  a1678-8060