Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2003-8-20
pubmed:abstractText
The interaction between TCR and peptide-MHC (pMHC) complexes is crucial for the activation of T cells as well as for positive and negative selection in the thymus. The kinetics and affinity of this interaction and the densities of TCR and pMHC complexes on the cell surface are determining factors for different outcomes during thymic selection. In general, it is thought that agonist pMHC, which cause negative selection, have higher affinities and, in particular, slower off-rates than partial or weak agonists and antagonists, which cause positive selection. In this study, we have used pMHC tetramers to investigate the kinetics of TCR-pMHC interaction for agonist, weak agonist, and antagonist ligands of the anti-lymphocytic choriomeningitis virus P14 TCR. Kinetics determined on the cell surface may be biologically more relevant than methods using soluble proteins. We can distinguish between agonists and weak agonists or antagonists based on the half-life and the avidity of tetramer-TCR interaction. Furthermore, we show that a weak agonist self-peptide that positively selects P14 TCR(+) thymocytes has a tetramer half-life and avidity only slightly weaker than strong agonists. We show that, in fact, it can act as quite a strong agonist, but that its poor ability to stabilize MHC causes it instead to have a weak agonist phenotype.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
171
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2427-34
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:12928390-Amino Acid Substitution, pubmed-meshheading:12928390-Animals, pubmed-meshheading:12928390-Antigen Presentation, pubmed-meshheading:12928390-Binding, Competitive, pubmed-meshheading:12928390-Cell Line, Tumor, pubmed-meshheading:12928390-Cell Membrane, pubmed-meshheading:12928390-Dose-Response Relationship, Immunologic, pubmed-meshheading:12928390-Down-Regulation, pubmed-meshheading:12928390-Epitopes, T-Lymphocyte, pubmed-meshheading:12928390-H-2 Antigens, pubmed-meshheading:12928390-Half-Life, pubmed-meshheading:12928390-Kinetics, pubmed-meshheading:12928390-Lymphocyte Activation, pubmed-meshheading:12928390-Mice, pubmed-meshheading:12928390-Mice, Inbred C57BL, pubmed-meshheading:12928390-Mice, Transgenic, pubmed-meshheading:12928390-Oligopeptides, pubmed-meshheading:12928390-Protein Binding, pubmed-meshheading:12928390-Receptors, Antigen, T-Cell, pubmed-meshheading:12928390-T-Lymphocytes
pubmed:year
2003
pubmed:articleTitle
TCR binding kinetics measured with MHC class I tetramers reveal a positive selecting peptide with relatively high affinity for TCR.
pubmed:affiliation
Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't