GENERATION AND CHARACTERIZATION OF GP100 PEPTIDE-SPECIFIC NK-T CELL CLONES

MHC-restricted cytotoxic T lymphocytes (CTLs) specific for antigens ex pressed by malignant cells are important components of immune response s against human cancer. Peripheral blood monocytes of HLA-A2(+) health y donors were used to induce dendritic cells (DCs) by granulocyte-macr ophage colony-stimulating factor and interleukin-4 and loaded with a g p100 peptide (YLEPGPVTA). By applying these peptide-loaded DCs, a CTL line that displayed high cytotoxic reactivity with peptide-loaded targ et cells was generated. A total of II gp100 peptide-specific CTL clone s were generated from this cell line. Several of these CTL clones were studied in detail. Of particular interest was clone CTL-45, which, co ntrary to the parental cell line, displayed strong NK activity and, by flow-cytometric analysis, revealed a CD3(+), TCR BV 17, CD8(+) and CD 56(+) phenotype. This clone was strictly peptide-specific and effectiv ely killed a panel of melanoma cells expressing HLA-A2 and gp100. Tumo r-specific T cells with this kind of dual function are potentially of great clinical importance as they have a backup mechanism that may go into action when tumor cells escape specific killing by losing their H LA-class 1 molecules. (C) 1998 Wiley-Liss, Inc.