title: Identification and characterization of the ESAT-6 homologue of Mycobacterium leprae and T-cell cross-reactivity with Mycobacterium tuberculosis.
abstract: In this paper we describe identification and characterization of Mycobacterium leprae ESAT-6 (L-ESAT-6), the homologue of M. tuberculosis ESAT-6 (T-ESAT-6). T-ESAT-6 is expressed by all pathogenic strains belonging to the M. tuberculosis complex but is absent from virtually all other mycobacterial species, and it is a promising antigen for immunodiagnosis of tuberculosis (TB). Therefore, we analyzed whether L-ESAT-6 is a similarly powerful tool for the study of leprosy by examining T-cell responses against L-ESAT-6 in leprosy patients, TB patients, and exposed or nonexposed healthy controls from areas where leprosy and TB are endemic and areas where they are not endemic. L-ESAT-6 was recognized by T cells from leprosy patients, TB patients, individuals who had contact with TB patients, and healthy individuals from an area where TB and leprosy are endemic but not by T cells from individuals who were not exposed to M. tuberculosis and M. leprae. Moreover, leprosy patients who were not responsive to M. leprae failed to respond to L-ESAT-6. A very similar pattern was obtained with T-ESAT-6. These results show that L-ESAT-6 is a potent M. leprae antigen that stimulates T-cell-dependent gamma interferon production in a large proportion of individuals exposed to M. leprae. Moreover, our results suggest that there is significant cross-reactivity between T-ESAT-6 and L-ESAT-6, which has implications for the use of ESAT-6 as tool for diagnosis of leprosy and TB in areas where both diseases are endemic.
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands. ageluk@lumc.nl
authors.forename: Annemieke
authors.initials: A
authors.lastname: Geluk
authors.forename: Krista E
authors.initials: KE
authors.lastname: van Meijgaarden
authors.forename: Kees L M C
authors.initials: KL
authors.lastname: Franken
authors.forename: Yanri W
authors.initials: YW
authors.lastname: Subronto
authors.forename: Brigitte
authors.initials: B
authors.lastname: Wieles
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Arend
authors.forename: Elizabeth P
authors.initials: EP
authors.lastname: Sampaio
authors.forename: Tjitske
authors.initials: T
authors.lastname: de Boer
authors.forename: William R
authors.initials: WR
authors.lastname: Faber
authors.forename: Ben
authors.initials: B
authors.lastname: Naafs
authors.forename: Tom H M
authors.initials: TH
authors.lastname: Ottenhoff
mesh_terms: D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000032:analysis / Q000737:chemistry / Q000276:immunology*; D001426:Bacterial Proteins; D003429:Cross Reactions; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007918:Leprosy / Q000276:immunology; D008969:Molecular Sequence Data; D009166:Mycobacterium leprae / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D007371:Interferon-gamma