Isolation and characterization of the genes of pathogenic mycobacteria that express antigens for T cell reactivity.

Tuberculosis and leprosy are caused by Mycobacterium tuberculosis and Mycobacterium leprae, respectively. Identification and characterization of the genes expressing proteins that stimulate Th1-type cells is required to understand the mechanisms involved in protection from mycobacterial diseases. We isolated several recombinant genes from recombinant DNA libraries that expressed antigens recognized by well-characterized monoclonal antibodies. We first used these isolated recombinants to show that many of these genes expressed antigens with T cell reactivity. Most of the genes in the lambda gt11 system were truncated at the amino terminus. Full-length genes were isolated from libraries in other systems and sequenced. Four of the full-length genes were homologous to heat shock proteins of eukaryotes and prokaryotes. We also screened the recombinant DNA libraries directly with T cell probes for antigens that may not be recognized by antibodies. We isolated one gene expressing an epitope recognized by T cells reactive with M. tuberculosis, M. leprae, and M. bovis BCG but not with other mycobacteria. All recombinant proteins were presented to T cells in association with multiple HLA-DR molecules. The responding T cells were the Th1 type with long-lasting memory. The protein products of these genes, either by themselves or expressed in suitable vaccines, may be used to protect against tuberculosis and leprosy.