Source:http://linkedlifedata.com/resource/pubmed/id/17464507
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
11
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| pubmed:dateCreated |
2007-8-27
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| pubmed:abstractText |
By the use of a neural network capable of performing quantitative predictions of peptides binding to HLA-A*0201 molecules, we identified a number of nonamer peptides derived from the catalytic subunit of telomerase, human telomerase reverse transcriptase (hTERT). Five nonimmunogenic peptides with measured binding affinities for HLA-A*0201 ranging from 155 to 1,298 nM were modified at the P1, P2 and P9 positions, respectively, to achieve stronger HLA-A*0201 binding. One peptide, mp30-38 (mp30), with an L to V substitution at position 9 was subsequently found to be immunogenic in mp30 immunized HLA-A*0201/H2K(b) or HHD transgenic mice. The T cell reactivity obtained was directed against both the mp30 and against the unmodified p30. Anti-mp30 specific T cells generated in HLA-A*0201 transgenic mice were dependent on TCR-CD8/MHC-I alpha3 binding and therefore not capable of recognizing mp30-pulsed human HLA-A*0201(+) cells or murine HLA-A*0201 transfectants. In order to show reactivity against naturally processed peptide in human tumor cells, an hTERT positive HLA-A*0201 negative colon carcinoma cell line (CCL220) was transfected with an HLA-A*0201/H2K(b) cDNA construct and used as target in ELISPOT and cytotoxicity assays. The data show that T cells from mp30 immunized HHD transgenic mice react specifically against the CCL220 transfectant indicating that p30 is naturally processed. In conclusion, we have identified a new CTL HLA-A*0201 restricted hTERT epitope, which is now, included in an ongoing phase 2 vaccine trial of patients with disseminated cancer.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Epitopes, T-Lymphocyte,
http://linkedlifedata.com/resource/pubmed/chemical/HLA-A*02:01 antigen,
http://linkedlifedata.com/resource/pubmed/chemical/HLA-A Antigens,
http://linkedlifedata.com/resource/pubmed/chemical/HLA-A2 Antigen,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Telomerase
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| pubmed:status |
MEDLINE
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| pubmed:month |
Nov
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| pubmed:issn |
0340-7004
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
56
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1755-63
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| pubmed:dateRevised |
2011-11-17
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| pubmed:meshHeading |
pubmed-meshheading:17464507-Amino Acid Sequence,
pubmed-meshheading:17464507-Amino Acid Substitution,
pubmed-meshheading:17464507-Animals,
pubmed-meshheading:17464507-Antigen Presentation,
pubmed-meshheading:17464507-Blotting, Western,
pubmed-meshheading:17464507-CD8-Positive T-Lymphocytes,
pubmed-meshheading:17464507-Cell Line, Tumor,
pubmed-meshheading:17464507-Epitopes, T-Lymphocyte,
pubmed-meshheading:17464507-HLA-A Antigens,
pubmed-meshheading:17464507-HLA-A2 Antigen,
pubmed-meshheading:17464507-Humans,
pubmed-meshheading:17464507-Mice,
pubmed-meshheading:17464507-Mice, Transgenic,
pubmed-meshheading:17464507-Molecular Sequence Data,
pubmed-meshheading:17464507-Peptide Fragments,
pubmed-meshheading:17464507-Protein Binding,
pubmed-meshheading:17464507-T-Lymphocytes, Cytotoxic,
pubmed-meshheading:17464507-Telomerase
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| pubmed:year |
2007
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| pubmed:articleTitle |
Identification of a new hTERT-derived HLA-A*0201 restricted, naturally processed CTL epitope.
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| pubmed:affiliation |
Laboratory of Cellular Immunology, Department of International Health, Immunology and Microbiology, The Panum Institute, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen N, Denmark.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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