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Titolo:
A TGF beta RII frameshift-mutation-derived CTL epitope recognised by HLA-A2-restricted CD8(+) T cells
Autore:
Saeterdal, I; Gjertsen, MK; Straten, P; Eriksen, JA; Gaudernack, G;
Indirizzi:
Univ Oslo, Norwegian Radium Hosp, Dept Immunol, Sect Immunotherapy, N-0310Oslo, Norway Univ Oslo Oslo Norway N-0310 nol, Sect Immunotherapy, N-0310Oslo, Norway Danish Canc Soc, Div Canc Biol, Dept Tumor Cell Biol, Copenhagen, Denmark Danish Canc Soc Copenhagen Denmark Tumor Cell Biol, Copenhagen, Denmark Hydro Res Ctr, Porsgrunn, Norway Hydro Res Ctr Porsgrunn NorwayHydro Res Ctr, Porsgrunn, Norway
Titolo Testata:
CANCER IMMUNOLOGY IMMUNOTHERAPY
fascicolo: 9, volume: 50, anno: 2001,
pagine: 469 - 476
SICI:
0340-7004(200111)50:9<469:ATBRFC>2.0.ZU;2-J
Fonte:
ISI
Lingua:
ENG
Soggetto:
GROWTH-FACTOR-BETA; MATURE DENDRITIC CELLS; COLORECTAL-CANCER; MICROSATELLITE INSTABILITY; II RECEPTOR; LINES; CARCINOMAS; EXPRESSION; SELECTION; TUMORS;
Keywords:
CTL epitope; microsatellite instability; TGF beta RII frameshift mutation;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
26
Recensione:
Indirizzi per estratti:
Indirizzo: Saeterdal, I Univ Oslo, Norwegian Radium Hosp, Dept Immunol, Sect Immunotherapy, N-0310Oslo, Norway Univ Oslo Oslo Norway N-0310 unotherapy, N-0310Oslo, Norway
Citazione:
I. Saeterdal et al., "A TGF beta RII frameshift-mutation-derived CTL epitope recognised by HLA-A2-restricted CD8(+) T cells", CANCER IMMU, 50(9), 2001, pp. 469-476

Abstract

Microsatellite instability (MSI) is recognised as genome-wide alterations in repetitive DNA sequences caused by defects in the DNA mismatch repair machinery. Such mutation patterns have been found in almost all analysed malignancies from patients with hereditary non-polyposis colorectal cancer, andin approximately 15% of sporadic colorectal cancers. In cancers with the MSI phenotype, micro satellite-like sequences in coding regions of various cancer-related genes, including transforming growth factor beta receptor type II (TGF beta RII), are targets for mutations. The TGF beta RII gene harbours a 10-bp polyadenine tract, and mutations within this region are found in 90% of colorectal cancers with MSI. The frameshift mutations result in new amino acid sequences in the C-terminal part of the proteins, prematurely terminating where a novel stop codon appears. In this study we have defineda new cytotoxic T lymphocyte (CTL) epitope (RLSSCVPVA), carrying a good HLA-A*0201 binding motif. and resulting from the most common frameshift mutation in TGF beta RII. A CTL line and several CTL clones were generated from an HLA-A2(+) normal donor by repeated stimulation of T cells with dendriticcells pulsed with the peptide. One of the CTL clones was able to kill an HLA-A2(+) colon cancer cell line harbouring mutant TGF beta RII. This epitope may be a valuable component in cancer vaccines directed at MSI-positive carcinomas.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 24/09/20 alle ore 07:53:41