Linked Life Data

14523945

Source:http://linkedlifedata.com/resource/pubmed/id/14523945

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2003-10-2
pubmed:abstractText
The advent in recent years of the application of tetrameric arrays of class I peptide-MHC complexes now enables us to detect and study rare populations of antigen-specific CD8+ T cells. However, available methods cannot visualize or determine the number and distribution of these TCR ligands on individual cells or detect antigen-presenting cells (APCs) in tissues. Here we describe a new approach that enables study of human class I peptide-MHC ligand-presentation as well as TCR-peptide-MHC interactions. Such studies are facilitated by applying novel tools in the form of peptide-specific, HLA-A2-restricted human recombinant antibodies directed toward a large variety of tumor-associated as well as viral T-cell epitope peptides. Using a large human antibody phage display library, a large panel of recombinant antibodies that are specific for a particular peptide-MHC class I complex in a peptide-dependent, MHC-restricted manner was isolated. These antibodies were used to directly visualize the specific MHC-peptide complex on tumor cells, antigen-presenting cells or virus-infected cells by flow cytometry. They enabled direct quantitation of the number of MHC-peptide complexes as well as in situ detection of the complex on the surface of APCs after naturally occurring active intracellular processing of the cognate antigen. These studies will enable also the development of a new class of targeting molecules to deliver drugs or toxins to tumor or virus-infected cells. Thus, we demonstrate our ability to transform the unique fine specificity but low intrinsic affinity of TCRs into high-affinity soluble antibody molecules endowed with a TCR-like specificity toward human tumor or viral epitopes. These molecules may prove to be crucial useful tools for studying MHC class I antigen presentation in health and disease as well as for therapeutic purposes in cancer, infectious diseases and autoimmune disorders.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0952-3499
pubmed:author
pubmed:copyrightInfo
Copyright 2003 John Wiley & Sons, Ltd.
pubmed:issnType
Print
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
324-32
pubmed:dateRevised
2005-11-16
pubmed:meshHeading
pubmed:articleTitle
Recombinant antibodies with MHC-restricted, peptide-specific, T-cell receptor-like specificity: new tools to study antigen presentation and TCR-peptide-MHC interactions.
pubmed:affiliation
Faculty of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel.
pubmed:publicationType
Journal Article, Review