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Protective immunity to Mycobacterium tuberculosis is poorly understood, but mounting evidence, at least in animal models, implicates major histocompatibility complex class I-restricted CD8+ T cells as an essential component. By using a highly sensitive assay for single cell interferon gamma release, we screened an array of M. tuberculosis antigen-derived peptides congruent with HLA class I allele-specific motifs. We identified CD8+ T cells specific for epitopes in the early secretory antigenic target 6 during active tuberculosis, after clinical recovery and in healthy contacts. Unrestimulated cells exhibited peptide-specific interferon gamma secretion, whereas lines or clones recognized endogenously processed antigen and showed cytolytic activity. These results provide direct evidence for the involvement of CD8+ cytotoxic T lymphocytes in host defense against M. tuberculosis in humans and support current attempts to generate protective cytotoxic T lymphocyte responses against M. tuberculosis by vaccination.

Original publication




Journal article


Proc Natl Acad Sci U S A

Publication Date





270 - 275


Adult, Amino Acid Sequence, Antigens, Bacterial, Bacterial Proteins, CD8-Positive T-Lymphocytes, Histocompatibility Testing, Humans, Interferon-gamma, Molecular Sequence Data, Mycobacterium tuberculosis, T-Lymphocytes, Regulatory, Tuberculosis