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. 2004 Apr;111(4):462-71. doi: 10.1111/j.0019-2805.2004.01839.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antibodies, Bacterial / biosynthesis
  • Antigens, Bacterial / genetics
  • Antigens, Bacterial / immunology
  • B-Lymphocytes / immunology
  • Bacterial Proteins / genetics
  • Bacterial Proteins / immunology
  • Chaperonin 10 / genetics
  • Chaperonin 10 / immunology*
  • Cytokines / biosynthesis
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / immunology
  • Humans
  • Immunoglobulin G / biosynthesis
  • Leprosy / immunology*
  • Lymphocyte Activation / immunology
  • Molecular Sequence Data
  • Mycobacterium leprae / immunology*
  • Mycobacterium tuberculosis / immunology*
  • Peptide Fragments / immunology
  • T-Lymphocytes / immunology
  • Tuberculosis, Pulmonary / immunology*

Substances

  • Antibodies, Bacterial
  • Antigens, Bacterial
  • Bacterial Proteins
  • Chaperonin 10
  • Cytokines
  • Heat-Shock Proteins
  • Immunoglobulin G
  • Peptide Fragments
  • groES protein, Mycobacterium tuberculosis