The invention provides novel Class I HLA-A2 and Class II HLA-DR4-restricted epitopes and methods for their use in detecting T-cells in peripheral blood specific for infection or latency of mycobacterial infection, including M. tuberculosis and M. leprae as others. For example, methods for diagnosing the presence of infection or exposure by M. tuberculosis utilize multimers of HLA monomers or modified monomers having a bound HLA-binding peptide to perform high throughput screening of patient PBLs. The methods can be used for monitoring the success of anti mycobacterial treatment in patients and to screen vaccines and drugs for effectiveness in treating or preventing exposure, infection and latency of mycobacteria in humans.