Human T‐ and B‐Cell Reactivity to the 16 kDa α‐Crystallin Protein of Mycobacterium tuberculosis

Abstract

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‐γ 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.

Genomic Approach to Identification of Mycobacterium bovis Diagnostic Antigens in Cattle

“…It has been identified as a highly expressed protein under hypoxic conditions mimicking dormancy (38) and upon macrophage infection (26) and is considered as such as a marker for latency (6). Its species specificity and early T-cell immunodominance in the mouse and human are well documented (43,45), and our novel cattle data are in agreement with these previous reports. Since HspX is expressed primarily during the late stage of infection, it has interesting potential as a diagnostic reagent.…”

Immune Responses to Mycobacterial Antigens in the Gambian Population: Implications for Vaccines and Immunodiagnostic Test Design

“…Surprisingly, while increased IFN-␥ responses to ␣-crystallin were observed for adults with a history of past BCG vaccination (41), no significant response to this antigen was detected in BCG-immunized infants 2 months after vaccination. The expression of ␣-crystallin and the development of a primary immune response to this antigen may be slower than that of other mycobacterial antigens in vivo (15).…”

“…We endeavored to evaluate their potential value as candidates for vaccine development or for the immunodiagnosis of tuberculosis. In areas with a low incidence of tuberculosis, these antigens had been previously shown to stimulate the production of IFN-␥ in tuberculin skin test-positive but not in tuberculin skin test-negative individuals (1,4,14,16,17,34,40,41). In this study, we confirm that all antigens are able to stimulate IFN-␥ production, but important differences were observed among groups exposed to different levels and types of mycobacteria, especially in the responses to CFP-10 and ␣-crystallin.…”

Latent Tuberculosis Infection: Myths, Models, and Molecular Mechanisms

“…DNA vaccines have shown promise in their ability to enhance the activity of antibiotic treatment and reduce reactivation of LTBI and transmission (323)(324)(325). Adjunctive immunotherapy with a DNA vaccine containing the LTBI marker ␣-crystallin (233,(328)(329)(330) reduces the duration of antibiotic treatment in chronically infected mice (331). Similarly, RUTI, a therapeutic vaccine comprising detoxified, fragmented M. tuberculosis cells delivered in liposomes, also has been shown to enhance the effect of short-course chemotherapy in animal models (326) and is currently being evaluated in clinical trials (327).…”