Specificity of T cells in human resistance to Mycobacterium tuberculosis infection

Secreted proteins are considered to have an important role in inducing resistance to Mycobacterium tuberculosis infection. We analyzed the proliferation of PBMC from five healthy tuberculin-positive individuals, four tuberculosis patients, and six tuberculin-negative healthy controls to the whole bacilli, the 38- and 10-kDa-secreted antigens, and the 65- and 71-kDa hsp. Comparing the proliferative responses between the two mycobacterial-secreted proteins, we have found that both the 38- and the 10-kDa antigens were recognized by PBMC from healthy tuberculin-positive individuals. However, the magnitude of the proliferation caused by the 10-kDa antigen was significantly higher (P < 0.005) than that with the 38-kDa protein. It was a finding of importance that proliferation to the 10-kDa antigen was comparable to that elicited by the whole bacilli. Characterization of proliferative responses toward the 10-kDa antigen demonstrates that human cells process the 10-kDa antigen prior to its recognition by T cells, and that this process might be through lysosomal pathways. These data confirm the strong T cell response against the M. tuberculosis 10-kDa antigen and demonstrate, for the first time, characterization of cellular activation toward this antigen. The magnitude of the proliferative responses to the 65-kDa hsp in the healthy tuberculin-positive subjects compared with tuberculosis patients was not significantly different (P > 0.01). Finally, PBMC from the healthy tuberculin-positive individuals did not recognize the M. tuberculosis 71-kDa hsp. In summary, human resistant cells to tuberculosis respond to different classes of antigens, including constitutive cell wall proteins, secreted antigens, and hsp.