02831nas a2200397   4500000000100000008004100001260001300042653002400055653002600079653002400105653001800129653002300147653001800170653001400188653002400202653001100226653002100237653001200258653002600270653002800296653002500324653003100349653002200380653001800402653002800420100001400448700001300462700001200475700001200487700001500499245021800514300001100732490000800743520166800751022001402419       2004                            d  c2004 Apr10aAmino Acid Sequence10aAntibodies, Bacterial10aAntigens, Bacterial10aB-Lymphocytes10aBacterial Proteins10aChaperonin 1010aCytokines10aHeat-Shock Proteins10aHumans10aImmunoglobulin G10aleprosy10aLymphocyte Activation10aMolecular Sequence Data10aMycobacterium leprae10aMycobacterium tuberculosis10aPeptide Fragments10aT-Lymphocytes10aTuberculosis, Pulmonary1 aHussain R1 aShahid F1 aZafar S1 aDojki M1 aDockrell H00aImmune 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.  a462-710 v1113 a<p>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.</p>  a0019-2805