title: Dominant recognition of a cross-reactive B-cell epitope in Mycobacterium leprae 10 K antigen by immunoglobulin G1 antibodies across the disease spectrum in leprosy.
abstract: Mycobacterium leprae-specific immunoglobulin G1 (IgG1) antibodies in patients with leprosy show a direct correlation with bacterial load (rho=0.748; P<0002) suggesting that IgG1 B-cell responses may be surrogate markers of disease progression. To investigate if this upregulation was a general feature of IgG1 responses to all M. leprae (ML) antigens, we analysed responses to several recombinant purified ML heat-shock proteins (HSP). Three recombinant HSPs (ML10 K, ML 18 K and ML 65 K) were tested for their ability to induce various IgG subclasses in patients with either the lepromatous (LL/BL, n=26) or tuberculoid form (BT/TT, n=39) of the disease as well as in healthy households (HC, n=14) and endemic controls (EC=19). Our major findings were: (1) selective augmentation of IgG1 antibody responses to ML10 K; (2) recognition of a restricted number of epitopes across the disease spectrum and healthy controls by IgG1 antibodies; (3) dominant recognition of cross-reactive epitopes which were common to both ML and MT 10 K. This response was not related to contamination with endotoxin. Epitope mapping using 15-mer overlapping peptides spanning the ML 10 000 MW revealed an immunodominant IgG1 binding peptide (aa41-55) in patients as well as healthy controls. This peptide is a shared epitope with M. tuberculosis 10 K suggesting that postswitched IgG1 B cells recognizing this epitope rather than naive B cells are being expanded.
authors.affiliation: Department of Microbiology, The Aga Khan University. PO Box 3500, Karachi, Pakistan.
authors.forename: R
authors.initials: R
authors.lastname: Hussain
authors.forename: H M
authors.initials: HM
authors.lastname: Dockrell
authors.forename: T J
authors.initials: TJ
authors.lastname: Chiang
mesh_terms: D000907:Antibodies, Bacterial / Q000096:biosynthesis; D000942:Antigens, Bacterial / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D003429:Cross Reactions; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology*; D007918:Leprosy / Q000276:immunology*; D009166:Mycobacterium leprae / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D000939:Epitopes; D007074:Immunoglobulin G; D011994:Recombinant Proteins