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

Mycobacterium leprau-specific immunoglobulin G1 (IgG1) antibodies in patien ts with leprosy show a direct correlation with bacterial load (rho = 0.748; P < 0002) suggesting that IgG1 B-cell responses may be surrogate markers o f disease progression. To investigate if this upregulation was a general fe ature of IgG1 responses to all M leprae (ML) antigens, we analysed response s to several recombinant purified;ML heat-shock proteins (HSP). Three recom binant 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/B L, 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 ML1 0 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 epitoyes which were common to both ML and MT 10 K. This r esponse was not related to contamination with endotoxin. Epitope mapping us ing 15-mer overlapping peptides spanning the ML 10 000 MW revealed an immun odominant IgG1 binding peptide (aa41-55) in patients as well as healthy con trols. 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.