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http://purl.uniprot.org/citations/19523231http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/19523231http://www.w3.org/2000/01/rdf-schema#comment"

Background

To develop peptide-based immunotherapy for osteosarcoma, we previously identified papillomavirus binding factor (PBF) as a CTL-defined osteosarcoma antigen in the context of HLA-B55. However, clinical application of PBF-based immunotherapy requires identification of naturally presented CTL epitopes in osteosarcoma cells in the context of more common HLA molecules such as HLA-A2.

Methods

Ten peptides with the HLA-A*0201 binding motif were synthesized from the amino acid sequence of PBF according to the BIMAS score and screened with an HLA class I stabilization assay. The frequency of CTLs recognizing the selected PBF-derived peptide was determined in peripheral blood of five HLA-A*0201+ patients with osteosarcoma using limiting dilution (LD)/mixed lymphocyte peptide culture (MLPC) followed by tetramer-based frequency analysis. Attempts were made to establish PBF-specific CTL clones from the tetramer-positive CTL pool by a combination of limiting dilution and single-cell sorting. The cytotoxicity of CTLs was assessed by 51Cr release assay.

Results

Peptide PBF A2.2 showed the highest affinity to HLA-A*0201. CD8+ T cells reacting with the PBF A2.2 peptide were detected in three of five patients at frequencies from 2 x 10-7 to 5 x 10-6. A tetramer-positive PBF A2.2-specific CTL line, 5A9, specifically lysed allogeneic osteosarcoma cell lines that expressed both PBF and either HLA-A*0201 or HLA-A*0206, autologous tumor cells, and T2 pulsed with PBF A2.2. Five of 12 tetramer-positive CTL clones also lysed allogeneic osteosarcoma cell lines expressing both PBF and either HLA-A*0201 or HLA-A*0206 and T2 pulsed with PBF A2.2.

Conclusion

These findings indicate that PBF A2.2 serves as a CTL epitope on osteosarcoma cells in the context of HLA-A*0201, and potentially, HLA-A*0206. This extends the availability of PBF-derived therapeutic peptide vaccines for patients with osteosarcoma."xsd:string
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http://purl.uniprot.org/citations/19523231http://purl.uniprot.org/core/author"Sato N."xsd:string
http://purl.uniprot.org/citations/19523231http://purl.uniprot.org/core/author"Wada T."xsd:string
http://purl.uniprot.org/citations/19523231http://purl.uniprot.org/core/author"Yamashita T."xsd:string
http://purl.uniprot.org/citations/19523231http://purl.uniprot.org/core/author"Kawaguchi S."xsd:string
http://purl.uniprot.org/citations/19523231http://purl.uniprot.org/core/author"Takahashi A."xsd:string
http://purl.uniprot.org/citations/19523231http://purl.uniprot.org/core/author"Torigoe T."xsd:string
http://purl.uniprot.org/citations/19523231http://purl.uniprot.org/core/author"Kano M."xsd:string
http://purl.uniprot.org/citations/19523231http://purl.uniprot.org/core/author"Tsukahara T."xsd:string
http://purl.uniprot.org/citations/19523231http://purl.uniprot.org/core/author"Murase M."xsd:string
http://purl.uniprot.org/citations/19523231http://purl.uniprot.org/core/author"Kaya M."xsd:string
http://purl.uniprot.org/citations/19523231http://purl.uniprot.org/core/author"Nagoya S."xsd:string
http://purl.uniprot.org/citations/19523231http://purl.uniprot.org/core/date"2009"xsd:gYear
http://purl.uniprot.org/citations/19523231http://purl.uniprot.org/core/name"J Transl Med"xsd:string
http://purl.uniprot.org/citations/19523231http://purl.uniprot.org/core/pages"44"xsd:string
http://purl.uniprot.org/citations/19523231http://purl.uniprot.org/core/title"HLA-A*0201-restricted CTL epitope of a novel osteosarcoma antigen, papillomavirus binding factor."xsd:string
http://purl.uniprot.org/citations/19523231http://purl.uniprot.org/core/volume"7"xsd:string
http://purl.uniprot.org/citations/19523231http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/19523231
http://purl.uniprot.org/citations/19523231http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/19523231
http://purl.uniprot.org/uniprot/#_A0A0A7C548-mappedCitation-19523231http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19523231
http://purl.uniprot.org/uniprot/#_A0A0A7C551-mappedCitation-19523231http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19523231
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