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.
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.
Hussain
Rabia
R
Department of Pathology and Microbiology, Aga Khan University, PO Box 3500, Karachi, Pakistan. rabia.hussain@aku.edu
Shahid
Firdaus
F
Zafar
Shahid
S
Dojki
Maqboola
M
Dockrell
Hazel M
HM
D000595:Amino Acid Sequence; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology; D018835:Chaperonin 10 / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D006360:Heat-Shock Proteins / Q000235:genetics / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D007918:Leprosy / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008969:Molecular Sequence Data; D009166:Mycobacterium leprae / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000276:immunology*
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D018835:Chaperonin 10; D016207:Cytokines; D006360:Heat-Shock Proteins; D007074:Immunoglobulin G; D010446:Peptide Fragments; C058749:groES protein, Mycobacterium tuberculosis