Abstract
Monoclonal antibodies restricted to Mycobacterium tuberculosis can measure epitope-specific antibody levels in a competition assay. Immunodominant epitopes were defined from clinical samples and related to the clinical spectrum of disease. Antibody to the immunodominant epitopes was associated with HLA-DR15. Occupational exposure showed a different response and was consistent with recognition of dormancy-related proteins and protection despite exposure to tuberculosis (TB). Studies in leprosy revealed the importance of immune deviation and the relationships between T and B cell epitopes. During treatment, antibody levels increased, epitope spreading occurred, but the affinity constants remained the same after further antigen exposure, suggesting constraints on the process of epitope selection. Epitope-specific antibody levels have a potential role as biomarkers for new vaccines which might prevent the progression of latent to active TB and as tools to measure treatment effects on subpopulations of tubercle bacilli.
Highlights
There are many unanswered questions in tuberculosis (TB) for which an understanding of both clinical aspects and the adaptive immune response is critical
Post-primary TB is characterized by an immune response to both cross-reactive antigens, as in the tuberculin response, and species-restricted antigens, such as those found in the RD1 sequence, namely esat-6 and cfp-10
The antibody epitopes on homologous proteins of M. leprae might overlap the binding site of the Mycobacterium tuberculosis (Mtb)-specific monoclonal antibodies (Mabs) sufficiently to inhibit binding, there being no homolog of the M. leprae 35-kDa antigen in Mtb
Summary
There are many unanswered questions in tuberculosis (TB) for which an understanding of both clinical aspects and the adaptive immune response is critical. More than 80% of patients with this form of disease recognize epitopes of the 38-kDa lipoprotein antigen (Rv0934, Antigen 5, Antigen 78, PstS1, PhoS) and epitope-specific antibody correlates well with antibody levels to the purified antigen [8,9,10,11,12]. The extent of pulmonary disease has shown a positive association with IgG antibody to the 38-kDa antigen, levels of which were higher in the few who died from TB [13].
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