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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
1999-6-3
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pubmed:abstractText |
Cytotoxic T cells (CTL) recognize short peptides that are derived from the proteolysis of endogenous cellular proteins and presented on the cell surface as a complex with MHC class I molecules. CTL can recognize single amino acid substitutions in proteins, including those involved in malignant transformation. The mutated sequence of an oncogene may be presented on the cell surface as a peptide, and thus represents a potential target antigen for tumour therapy. The p21ras gene is mutated in a wide variety of tumours and since the transforming mutations result in amino acid substitutions at positions 12, 13 and 61 of the protein, a limited number of ras peptides could potentially be used in the treatment of a wide variety of malignancies. A common substitution is Val for Gly at position 12 of p21ras. In this study, we show that the peptide sequence from position 5 to position 14 with Val at position 12-ras p5-14 (Val-12)-has a motif which allows it to bind to HLA-A2.1. HLA-A2.1-restricted ras p5-14 (Val-12)-specific CTL were induced in mice transgenic for both HLA-A2.1 and human beta2-microglobulin after in vivo priming with the peptide. The murine CTL could recognize the ras p5-14 (Val-12) peptide when they were presented on both murine and human target cells bearing HLA-A2.1. No cross-reactivity was observed with the native peptide ras p5-14 (Gly-12), and this peptide was not immunogenic in HLA-A2.1 transgenic mice. This represents an interesting model for the study of an HLA-restricted CD8 cytotoxic T cell response to a defined tumour antigen in vivo.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/10337009-1282032,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10337009-1383348,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10337009-1639630,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10337009-1670640,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10337009-1713253,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10337009-1714934,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10337009-1744590,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10337009-1910680,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10337009-2005390,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10337009-2295089,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10337009-2411422,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10337009-2464645,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10337009-2568889,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10337009-2676561,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10337009-3128632,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10337009-3304147,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10337009-3522223,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10337009-7683038,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10337009-7729952,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10337009-7734422,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10337009-8240732,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10337009-8316825,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10337009-8340941,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10337009-8617315,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10337009-9079825,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10337009-9311595
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0009-9104
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
116
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
214-9
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:10337009-Amino Acid Sequence,
pubmed-meshheading:10337009-Animals,
pubmed-meshheading:10337009-Binding, Competitive,
pubmed-meshheading:10337009-Cell Line,
pubmed-meshheading:10337009-HLA-A2 Antigen,
pubmed-meshheading:10337009-Humans,
pubmed-meshheading:10337009-Immunophenotyping,
pubmed-meshheading:10337009-Mice,
pubmed-meshheading:10337009-Mice, Inbred C57BL,
pubmed-meshheading:10337009-Mice, Inbred CBA,
pubmed-meshheading:10337009-Mice, Transgenic,
pubmed-meshheading:10337009-Molecular Sequence Data,
pubmed-meshheading:10337009-Mutation,
pubmed-meshheading:10337009-Peptide Fragments,
pubmed-meshheading:10337009-Proto-Oncogene Proteins p21(ras),
pubmed-meshheading:10337009-T-Lymphocytes, Cytotoxic
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pubmed:year |
1999
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pubmed:articleTitle |
Induction in transgenic mice of HLA-A2.1-restricted cytotoxic T cells specific for a peptide sequence from a mutated p21ras protein.
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pubmed:affiliation |
Institute of Biochemistry and Swiss Institute for Experimental Cancer Research, University of Lausanne, Epalinges, Switzerland.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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