Brefeldin A blocks the cytotoxicity of T cell receptor alpha/beta and gamma/delta cytotoxic T lymphocyte clones reacting against human autologous cancer cells.
We studied the effector mechanism of T cell receptor (TCR) alpha/beta- and gamma/delta-type cytotoxic T lymphocyte (CTL) clones that react with human autologous tumor cells. Treatment of tumor cells with a fungal antibacterial reagent, brefeldin A (BFA), resulted in the inhibition of cytotoxicity of an autologous tumor (HST-2)-specific CD8+ TCR alpha/beta-type CTL, TcHST-2. Other anti-metabolites such as chloroquine, cycloheximide and colchicine did not affect the cytotoxicity. The cell-surface antigen expression, including MHC class I molecules, was not influenced by BFA treatment. Furthermore, BFA did not influence the cytotoxicity of lymphokine-activated killer cells and natural killer cells. Since BFA blocks the transport of peptides from endoplasmic reticulum to the Golgi apparatus, the above data suggest that BFA could affect washing out of the peptide fragments from the MHC class I groove. Consequently, target tumor cells were protected from killing by CTL. Moreover, we obtained a CD4-, 8-, TCR gamma/delta-type (V delta 1+) CTL clone, TcHOT, that reacts against an autologous ovarial carcinoma, HOT. BFA could also inhibit this cytotoxicity, and it is likely that different presenting molecules other than MHC class I proteins participate in the cytotoxicity of this TCR gamma/delta-type CTL. These studies suggest that both TCR alpha/beta- and gamma/delta-type CTL may require antigenic peptides that are most likely derived from the BFA-sensitive, intracellular endogenous target proteins.
Wada
Y
Y
Department of Pathology, Sapporo Medical University School of Medicine.
Ikeda
H
H
Ueda
D
D
Ohta
M
M
Takahashi
S
S
Hirata
K
K
Sato
N
N
Kikuchi
K
K
D020126:Brefeldin A; D002738:Chloroquine / Q000494:pharmacology; D003078:Colchicine / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D003517:Cyclopentanes / Q000494:pharmacology*; D003601:Cytotoxicity Tests, Immunologic; D006801:Humans; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000187:drug effects*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000187:drug effects*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D003517:Cyclopentanes; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D020126:Brefeldin A; D002738:Chloroquine; D003513:Cycloheximide; D003078:Colchicine