Relative Importance of Defined Mycobacterium Tuberculosis Antigens in the T Cell Recognition Repertoire of Latently Infected Individuals not Progressing to Active Disease.

Abstract

In this study, we have mapped the relative importance of well-defined recombinantly expressed Mycobacterium tuberculosis antigens in the T cell recognition repertoire of latently infected individuals not progressing to active disease. Peripheral blood mononuclear cells from healthy latently infected long term non-progressors were screened for antigen-induced proliferation and Th1 cytokine, Interferon- (IFN-γ) responses. The panel of antigens tested showed a clear spectrum of responsiveness and lead to the identification of a subgroup of frequently recognized antigens (MPT59, CFP7, CFP10, CFP21, TB37.6 /PPE68, ESAT-6, MPT51, and DnaK) with a high cellular response level as measured in both proliferation and IFN-γ assays. Among a subgroup of antigens also screened for responses in tuberculosis patients, CFP21 was identified as differentially recognized in non-progressors. For both cellular assays, we found a positive correlation between responder frequency and magnitude of response. A significant correlation between the level of antigen-specific proliferation and INF-γ secretion was also observed. We have identified a defined set of M. tuberculosis antigens frequently recognized by T cells at a high response level from latently infected long term non-progressors which warrant further investigation for a potential role in immune regulation and protection against progression to active disease.