Linked Life Data

14581345

Source:http://linkedlifedata.com/resource/pubmed/id/14581345

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
2003-10-28
pubmed:abstractText
An effective tumor vaccine may require the induction of both CTL and T-helper (Th) cell responses against tumor-associated antigens. Human telomerase reverse transcriptase (hTERT) is highly expressed in >85% of cancer cells and thus is a potential target for tumor vaccines. We therefore sought to identify promiscuous Th epitopes in hTERT, which can be presented by more than one MHC class II allele. Each of 10 peptides derived from hTERT that were predicted to bind to MHC class II molecules was found to be able to induce primary human T-cell responses in vitro. We then established CD4(+) T-cell clones specific for these peptides and found that only hTERT(766) (LTDLQPYMRQFVAHL)-specific CD4(+) Th cells were effective in recognizing naturally processed hTERT antigen. We further found that the naturally processed epitopes hTERT(766) and hTERT(672) (which was identified previously) were promiscuous and capable of inducing CD4(+) T-cell responses in the context of several commonly found HLA-DR alleles, including DR1, DR7, and DR15 for hTERT(672), and DR4, DR11, and DR15 for hTERT(766). We further demonstrated that immunization of humanized HLA-DR4 transgenic mice with hTERT(766) peptide elicited antigen-specific Th responses that can recognize the antigenic peptides derived from hTERT protein and various hTERT-positive tumors, such as breast cancer, melanoma, and leukemia. It was also shown that T-cell precursors specific for the naturally processed epitopes are part of the T-cell repertoires in healthy donors and prostate cancer patients. Thus, these promiscuous, naturally processed Th epitopes in hTERT could be used to develop improved cancer vaccines through the simultaneous stimulation of CTL and Th cells against a broad spectrum of hTERT-positive tumors.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1078-0432
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4743-55
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:14581345-Alleles, pubmed-meshheading:14581345-Animals, pubmed-meshheading:14581345-Antibodies, Monoclonal, pubmed-meshheading:14581345-Antigens, pubmed-meshheading:14581345-CD4-Positive T-Lymphocytes, pubmed-meshheading:14581345-Cell Division, pubmed-meshheading:14581345-Cell Line, pubmed-meshheading:14581345-Cell Line, Tumor, pubmed-meshheading:14581345-Cell Separation, pubmed-meshheading:14581345-Cells, Cultured, pubmed-meshheading:14581345-DNA-Binding Proteins, pubmed-meshheading:14581345-Dendritic Cells, pubmed-meshheading:14581345-Dose-Response Relationship, Drug, pubmed-meshheading:14581345-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:14581345-Epitopes, pubmed-meshheading:14581345-Flow Cytometry, pubmed-meshheading:14581345-HLA-DR Antigens, pubmed-meshheading:14581345-Histocompatibility Antigens Class II, pubmed-meshheading:14581345-Humans, pubmed-meshheading:14581345-Insects, pubmed-meshheading:14581345-Mice, pubmed-meshheading:14581345-Mice, Transgenic, pubmed-meshheading:14581345-Peptides, pubmed-meshheading:14581345-RNA, Messenger, pubmed-meshheading:14581345-T-Lymphocytes, pubmed-meshheading:14581345-Telomerase
pubmed:year
2003
pubmed:articleTitle
Human telomerase reverse transcriptase-specific T-helper responses induced by promiscuous major histocompatibility complex class II-restricted epitopes.
pubmed:affiliation
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas 77030, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't