Examination of CD8(+) T cell function in humans using MHC class I tetramers: Similar cytotoxicity but variable proliferation and cytokine production among different clonal CD8(+) T cells specific to a single viral epitope

Following infection by human T cell lymphotrophic virus-I (HTLV-I), high fr equencies of polyclonal Tax11-19-reactive CD8(+) T cells can be detected in the peripheral blood. To investigate whether there are differences in the effector functions of these cells, we generated a panel of Tax11-19 reactiv e T cell clones by single cell sorting of HLA-A2/Tax11-19 tetramer binding CD8(+) T cells followed by repeated stimulation with PHA and IL-2, Examinat ion of the TCRs revealed 17 different T cell clones with unique clonal orig ins. Nine representative CD8(+) T cell clones showed a similar cytotoxic do se-response activity against Ag-pulsed target cells, even though they expre ss different TCRs, This cytotoxic effector function was not influenced by t he engagement of either CD28 or CD2 costimulatory molecules, In contrast to the cytotoxic activity, qualitatively different degrees of proliferative r esponse and cytokine secretion were observed among T cell clones of differe nt clonal origin, The induction of proliferation and cytokine secretion req uired the engagement of costimulatory molecules, particularly CD2-LFA-3 int eraction. These results indicate that functionally diverse, polyclonal CTL populations can be activated specific to a single immunodominant viral epit ope; they can manifest virtually identical cytotoxic effector function but have marked differences in proliferation and cytokine secretion.