Human T- and B-cell reactivity to the 16kDa alpha-crystallin protein of Mycobacterium tuberculosis

The attributes of immunodominance, predominant expression during mycobacterial dormancy and restriction to the Mycobacterium tuberculosis complex make the 16 kDa protein an important candidate for the study of the immune response in humans. We therefore investigated the relationship between T- and B-cell reactivity to the recombinant antigen and disease in a total of 127 subjects. The percentage of T-cell responders towards both the intact antigen and its permissively recognised peptide 16p91-110 was highest in healthy bacillus Calmette-Guérin (BCG)-sensitized controls (96% and 68%, respectively) and lowest in those with extensive untreated tuberculosis (26% and 18%) (P < 0.001). By contrast, antibody levels (ABT50 > 100) were highest in patients with extensive disease (46-50%) (P < 0.005). There was significantly higher production of IFN-gamma in the BCG-sensitized controls by comparison with untreated patients (P < 0.05), but complete antituberculous chemotherapy abolished this deficit in patients. The significance of these findings to immunodiagnosis and protective immunity is discussed.