02271nas a2200289   4500000000100000008004100001260001300042653002600055653002400081653001800105653002000123653001300143653001100156653002100167653001200188653002500200653003100225653002500256100001400281700001700295700001500312245016900327300001000496490000700506520145400513022001401967       1999                            d  c1999 Apr10aAntibodies, Bacterial10aAntigens, Bacterial10aB-Lymphocytes10aCross Reactions10aEpitopes10aHumans10aImmunoglobulin G10aleprosy10aMycobacterium leprae10aMycobacterium tuberculosis10aRecombinant Proteins1 aHussain R1 aDockrell H M1 aChiang T J00aDominant recognition of a cross-reactive B-cell epitope in Mycobacterium leprae 10 K antigen by immunoglobulin G1 antibodies across the disease spectrum in leprosy.  a620-70 v963 a<p>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.</p>  a0019-2805