Linked Life Data

11093159

Source:http://linkedlifedata.com/resource/pubmed/id/11093159

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2001-1-25
pubmed:abstractText
Low-affinity MHC class I-associated cryptic epitopes derived from self proteins overexpressed in a wide variety of human tumors or derived from antigens of viruses exhibiting a high mutation rate, could be interesting candidates for tumor and virus immunotherapy, respectively. However, identification of low-affinity MHC-associated epitopes comes up against their poor immunogenicity. Here we describe an approach that enhances immunogenicity of nonimmunogenic low-affinity HLA-A2.1-binding peptides. It consists of modifying their sequence by introducing a tyrosine in the first position (P1Y). P1Y substitution enhances affinity of HLA-A2.1-associated peptides without altering their antigenic specificity. In fact, P1Y variants of ten nonimmunogenic low-affinity peptides exhibited a 2.3- to 55-fold higher binding affinity and/or stabilized the HLA-A2.1 for at least 2 h more than the corresponding native peptides. More importantly, P1Y variants efficiently triggered in vivo native peptide-specific CTL which also recognized the corresponding naturally processed epitope. The possibility for generating CTL against any low-affinity HLA-A2.1-associated peptide provides us with the necessary tool for the identification of cryptic tumor and virus epitopes which could be used for peptide-based immunotherapy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0014-2980
pubmed:author
pubmed:issnType
Print
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3411-21
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
A general strategy to enhance immunogenicity of low-affinity HLA-A2. 1-associated peptides: implication in the identification of cryptic tumor epitopes.
pubmed:affiliation
INSERM 487, Villejuif, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't