Immune profiling of leprosy and tuberculosis patients to 15-mer peptides of Mycobacterium leprae and M tuberculosis GroES in a BCG vaccinated area: implications for development of vaccine and diagnostic reagents
Pathology and Laboratory Medicine
Mycobacterium leprae (ML) GroES has been shown to induce strong T cell responses in tuberculoid as well as in exposed healthy contacts of leprosy patients, and therefore this antigen has been the focus of study as a potential vaccine candidate. Paradoxically, we have shown that ML GroES also induces extremely high titres of IgG1 antibody in leprosy patients across the disease spectrum, a response associated with disease progression. IgG1 antibodies in leprosy also show a negative association with interferon-gamma, a critical T cell cytokine responsible for macrophage activation and intracellular killing of mycobacteria. We therefore queried if antibody and T cell responses were being evoked by different epitopes in ML GroES proteins. To address the issue of epitope recognition in mycobacterial diseases, we have analysed 16 peptides (15-mer peptides) spanning the entire ML and M. tuberculosis GroES protein in leprosy (n = 19) and tuberculosis (n = 9) patients and healthy endemic controls (n = 8). Our analysis demonstrates clearly that the dominant peptides evokingT cell and IgG subclass antibodies were different. The target of both T and B cell responses were cross-reactive epitopes in all groups. Differences in disease and healthy states related to the strength (mean intensity) of the T cell and antibody response. IgG1 and IgG3 antibodies were associated with disseminated disease and IgG 2 and IgG4 with disease limitation. Such comprehensive immune profiling of antigen-specific responses is critical to understanding the disease pathogenesis and also if these reagents are to be exploited for either diagnostic or vaccine purposes.
Dockrell, H. M.
(2004). Immune profiling of leprosy and tuberculosis patients to 15-mer peptides of Mycobacterium leprae and M tuberculosis GroES in a BCG vaccinated area: implications for development of vaccine and diagnostic reagents. Immunology, 111(4), 462-471.
Available at: https://ecommons.aku.edu/pakistan_fhs_mc_pathol_microbiol/874