Human leucocyte antigen-A2 restricted and Mycobacterium tuberculosis 19-kDa antigen-specific CD8(+) T-cell responses are oligoclonal and exhibit a T-cell cytotoxic type 2 response cytokine-secretion pattern

CD8(+) T cells can be grouped into two different types of secretory T lymph ocytes. based on the cytokine-secretion pattern upon antigen exposure: thos e with a T-cell cytotoxic type 1 response (TcI). which secrete interferon-g amma (IFN-gamma), or those with a T-cell cytotoxic type 2 response. which s ecrete interleukin (IL)-4 and IL-10. We examined the CD8(+) T-cell response directed against an immunodominant human leucocyte antigen (HLA)-A2-presen ted peptide derived from a 19-kDa Mycobacterium tuberculosis-associated ant igen. T cells were examined by functional analysis and by T-cell receptor ( TCR) complementarity-determining region 3 (CDR3)-spectratyping. which defin es the complexity or a T-cell response. T-cell stimulation with the immunod ominant VLTDGNPPEV epitope yielded a Tc2 (IL-4) cytokine-secretion pattern and resulted in oligoclonal expansion of TCR-variable beta chain (VB) famil ies, which differed from patient to patient. Generation of T-cell clones co rroborated the notion that the CD8(+) T-cell response directed against the HLA-A2-presented VLTDGNPPEV epitope leads to a Tc2 cytokine-secretion patte rn in CD8(+) T cells, as defined by IL-4 and granulocyte-macrophage colony- stimulating factor (GM-CSF) release. Characterization of the cytokine-secre tion profile in HLA-A2/VLTDGNPPEV-tetramer sorted T cells from patients wit h active tuberculosis supported this observation: peptide-specific T cells from three of three patients secreted IL-4 and only one of three patients p roduced IFN-gamma in response to the nominal target epitope. Permutation of this T-cell epitope may aid to elicit a qualitatively different CD8(+) T-c ell response in patients with M. tuberculosis infection.