title: Mycobacterium leprae virulence-associated peptides are indicators of exposure to M. leprae in Brazil, Ethiopia and Nepal.
abstract: 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.
authors.affiliation: Department of Infectious Diseases, University Medical Center, Leiden, The Netherlands.
authors.forename: Kidist
authors.initials: K
authors.lastname: Bobosha
authors.forename: Sheila Tuyet
authors.initials: ST
authors.lastname: Tang
authors.forename: Jolien J
authors.initials: JJ
authors.lastname: van der Ploeg-van Schip
authors.forename: Yonas
authors.initials: Y
authors.lastname: Bekele
authors.forename: Marcia V S B
authors.initials: MV
authors.lastname: Martins
authors.forename: Ole
authors.initials: O
authors.lastname: Lund
authors.forename: Kees L M C
authors.initials: KL
authors.lastname: Franken
authors.forename: Saraswoti
authors.initials: S
authors.lastname: Khadge
authors.forename: Maria Araci de Andrade
authors.initials: MA
authors.lastname: Pontes
authors.forename: Heitor de Sá
authors.initials: Hde S
authors.lastname: Gonçalves
authors.forename: Jemal
authors.initials: J
authors.lastname: Hussien
authors.forename: Pratibha
authors.initials: P
authors.lastname: Thapa
authors.forename: Chhatra B
authors.initials: CB
authors.lastname: Kunwar
authors.forename: Deanna A
authors.initials: DA
authors.lastname: Hagge
authors.forename: Abraham
authors.initials: A
authors.lastname: Aseffa
authors.forename: Maria Cristina Vidal
authors.initials: MC
authors.lastname: Pessolani
authors.forename: Geraldo M B
authors.initials: GM
authors.lastname: Pereira
authors.forename: Tom H M
authors.initials: TH
authors.lastname: Ottenhoff
authors.forename: Annemieke
authors.initials: A
authors.lastname: Geluk
mesh_terms: D001426:Bacterial Proteins / Q000276:immunology; D001938:Brazil; D019295:Computational Biology; D016207:Cytokines / Q000276:immunology*; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005002:Ethiopia; D006801:Humans; D009166:Mycobacterium leprae / Q000276:immunology / Q000302:isolation & purification / Q000472:pathogenicity* / Q000821:virology; D009390:Nepal; D010446:Peptide Fragments / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D014774:Virulence / Q000276:immunology*
chemical_list: D001426:Bacterial Proteins; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D010446:Peptide Fragments; D011994:Recombinant Proteins