Affinity, specificity and T-cell-receptor diversity of melanoma-specific CTL generated in vitro against a single tyrosinase epitope.
MHC-class-I-restricted cytotoxic T lymphocytes (CTL) specific for tumor-associated antigens expressed by malignant cells are important components of the immune response against cancer. Recently, tumor-specific CTL could be generated in vitro, with responding lymphocytes from the blood of healthy blood donors. In the present study, we confirm that peptide-specific stimulation in vitro can induce high-affinity CTL capable of recognizing tumor cells expressing the appropriate tumor antigen. These tyrosinase-specific CTL display a restricted usage of TCRAV and TCRBV gene segments but of diverse CDR3 regions, resulting in a distinct fine-specificity for each CTL clone. This suggests that, similar to in vivo priming, peptide-pulsed APC are capable of stimulating a T-cell response in vitro expressing a limited TCR repertoire against autologous tumors. The generated CTL can recognize their target structure with high affinity, and this correlates in part with tumor-cell lysis. This methodology may be used to treat melanoma patients with infusion of ex vivo-induced and -expanded CTL.
Visseren
M J
MJ
Department of Immunohematology and Blood Bank, Leiden University Hospital, The Netherlands.
van der Burg
S H
SH
Hawes
G E
GE
van der Voort
E I
EI
van den Elsen
P J
PJ
Melief
C J
CJ
D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D019673:Genes, T-Cell Receptor alpha; D019674:Genes, T-Cell Receptor beta; D014644:Genetic Variation; D015234:HLA-A Antigens / Q000276:immunology; D006801:Humans; D008545:Melanoma / Q000276:immunology*; D008969:Molecular Sequence Data; D014442:Monophenol Monooxygenase / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000939:Epitopes; D015234:HLA-A Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014442:Monophenol Monooxygenase