Functional and molecular analysis of T cell receptors used by pancreatic- and breast tumor- (mucin-) specific cytotoxic T cells.
We have previously reported that tumor-specific cytotoxic T lymphocytes (CTLs) derived from pancreatic and breast cancer patients recognize specific epitopes on the mucin polypeptide core. These CTLs recognize breast and pancreatic tumor cells in a major histocompatibility complex (MHC)-unrestricted fashion, and the lytic activity of these T cells is mediated through the T cell receptor (TCR). To characterize the TCR-mediated MHC-unrestricted CTL function, we used semiquantitative polymerase chain reaction (PCR) and cytofluorometry to analyze the TCR repertoire in CTL lines established from cancer patients and specific for mucin-expressing tumors. We found three TCR Vbeta genes, Vbeta9, Vbeta13.1. and Vbeta17, predominantly expressed in these functional cell lines, established either from one patient by stimulation with various mucin-expressing targets or from different patients. Sequencing of these preferentially used TCR genes unveiled usage of distinct Jbeta and Cbeta but a potentially interesting conservation of certain amino acids in the CDR3 region.
Kirii
Y
Y
Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pennsylvania 15261, USA.
Magarian-Blander
J
J
Alter
M D
MD
Kotera
Y
Y
Finn
O J
OJ
D000595:Amino Acid Sequence; D001483:Base Sequence; D001943:Breast Neoplasms / Q000276:immunology*; D006801:Humans; D008198:Lymph Nodes / Q000276:immunology; D009077:Mucins / Q000276:immunology*; D010190:Pancreatic Neoplasms / Q000276:immunology*; D018807:Polymorphism, Single-Stranded Conformational; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis* / Q000235:genetics* / Q000276:immunology; D017422:Sequence Analysis, DNA; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D009077:Mucins; D016693:Receptors, Antigen, T-Cell, alpha-beta