Antigen Provoking Gamma Interferon Production in Response to Mycobacterium bovis BCG and Functional Difference in T-Cell Responses to This Antigen between Viable and Killed BCG-Immunized Mice

It has been shown that gamma interferon (IFN-y)-producing CD4+ T cells, which are generated only by immunization with viable bacteria, exert a significant role in protective immunity against mycobacteria in mice. In this study, we have tried to determine the antigen recognized by the T cells in search of a possible protective antigen. T cells from viable Mycobacterium bovis BCG-immunized mice were stimulated with several antigens, and IFN-,y production was measured. Purified protein derivative and viable and killed BCG lysates caused significant IFN--y production, and almost the same level of IFN--y activity was detected in both groups stimulated with viable and killed BCG lysates. However, heat shock protein (HSP) 65 and HSP 70 were not a major antigen for IFN-,y production. The antigen provoking IFN-,y production is localized mainly in the membrane fraction of BCG cells, and the approximate molecular size was 18 kDa. On the other hand, T cells from killed BCG-immunized mice never responded to this antigen for IFN--y production, whereas they could mount a delayed-type hypersensitivity response. These results showed that the antigen provoking IFN--y production was present in killed as well as viable BCG. In addition to the antigen presentation by antigen-presenting cells, some kinds of differentiation factor (such as monokines) that are produced only by stimulation with viable cells seemed to be necessary for the development of IFN-y-producing T cells. Tuberculosis continues to be a major public health problem