Linked Life Data

19542454

Source:http://linkedlifedata.com/resource/pubmed/id/19542454

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2009-6-22
pubmed:databankReference
pubmed:abstractText
Protective T cell responses elicited along chronic human CMV (HCMV) infections are sometimes dominated by CD8 T cell clones bearing highly related or identical public TCR in unrelated individuals. To understand the principles that guide emergence of these public T cell responses, we have performed structural, biophysical, and functional analyses of an immunodominant public TCR (RA14) directed against a major HLA-A*0201-restricted HCMV Ag (pp65(495-503)) and selected in vivo from a diverse repertoire after chronic stimulations. Unlike the two immunodominant public TCRs crystallized so far, which focused on one peptide hotspot, the HCMV-specific RA14 TCR interacts with the full array of available peptide residues. The conservation of some peptide-MHC complex-contacting amino acids by lower-affinity TCRs suggests a shared TCR-peptide-MHC complex docking mode and supports an Ag-driven selection of optimal TCRs. Therefore, the emergence of a public TCR of an oligoclonal Ag-specific response after repeated viral stimulations is based on a receptor displaying a high structural complementarity with the entire peptide and focusing on three peptide hotspots. This highlights key parameters underlying the selection of a protective T cell response against HCMV infection, which remains a major health issue in patients undergoing bone marrow transplantation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1550-6606
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
183
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
430-7
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:19542454-Amino Acid Motifs, pubmed-meshheading:19542454-Clone Cells, pubmed-meshheading:19542454-Crystallography, X-Ray, pubmed-meshheading:19542454-Cytomegalovirus, pubmed-meshheading:19542454-Cytomegalovirus Infections, pubmed-meshheading:19542454-Epitopes, T-Lymphocyte, pubmed-meshheading:19542454-HLA-A Antigens, pubmed-meshheading:19542454-HLA-A2 Antigen, pubmed-meshheading:19542454-Humans, pubmed-meshheading:19542454-Immunodominant Epitopes, pubmed-meshheading:19542454-Lymphocyte Activation, pubmed-meshheading:19542454-Peptides, pubmed-meshheading:19542454-Phosphoproteins, pubmed-meshheading:19542454-Protein Binding, pubmed-meshheading:19542454-Receptors, Antigen, T-Cell, pubmed-meshheading:19542454-Viral Matrix Proteins, pubmed-meshheading:19542454-Virus Activation
pubmed:year
2009
pubmed:articleTitle
Structural bases for the affinity-driven selection of a public TCR against a dominant human cytomegalovirus epitope.
pubmed:affiliation
Institut de Biologie Structurale Jean-Pierre Ebel, CEA, CNRS, UJF, PSB, Grenoble, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't