Generation and characterization of gp100 peptide-specific NK-T cell clones.
MHC-restricted cytotoxic T lymphocytes (CTLs) specific for antigens expressed by malignant cells are important components of immune responses against human cancer. Peripheral blood monocytes of HLA-A2+ healthy donors were used to induce dendritic cells (DCs) by granulocyte-macrophage colony-stimulating factor and interleukin-4 and loaded with a gp100 peptide (YLEPGPVTA). By applying these peptide-loaded DCs, a CTL line that displayed high cytotoxic reactivity with peptide-loaded target cells was generated. A total of 11 gp100 peptide-specific CTL clones were generated from this cell line. Several of these CTL clones were studied in detail. Of particular interest was clone CTL-45, which, contrary to the parental cell line, displayed strong NK activity and, by flow-cytometric analysis, revealed a CD3+, TCR BV17, CD8+ and CD56+ phenotype. This clone was strictly peptide-specific and effectively killed a panel of melanoma cells expressing HLA-A2 and gp100. Tumor-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 HLA-class I molecules.
Saeterdal
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I
Institute for Cancer Research, The Norwegian Radium Hospital, University of Oslo. ingvil.saterdal@labmed.uio.no
thor Straten
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P
Myklebust
J H
JH
Kirkin
A F
AF
Gjertsen
M K
MK
Gaudernack
G
G
D000595:Amino Acid Sequence; D001483:Base Sequence; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D019673:Genes, T-Cell Receptor alpha; D019674:Genes, T-Cell Receptor beta; D006801:Humans; D007111:Immunity, Cellular; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000276:immunology*; D008545:Melanoma / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000276:immunology*; D010455:Peptides / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D058951:gp100 Melanoma Antigen
D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C548637:PMEL protein, human; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta; D058951:gp100 Melanoma Antigen