Source:http://linkedlifedata.com/resource/pubmed/id/17082606
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
10
|
| pubmed:dateCreated |
2006-11-3
|
| pubmed:abstractText |
TCRs exhibit a high degree of Ag specificity, even though their affinity for the peptide/MHC ligand is in the micromolar range. To explore how Ag specificity is achieved, we studied murine T cells expressing high-affinity TCRs engineered by in vitro evolution for binding to hemoglobin peptide/class II complex (Hb/I-Ek). These TCRs were shown previously to maintain Ag specificity, despite having up to 800-fold higher affinity. We compared the response of the high-affinity TCRs and the low-affinity 3.L2 TCR toward a comprehensive set of peptides containing single substitutions at each TCR contact residue. This specificity analysis revealed that the increase in affinity resulted in a dramatic increase in the number of stimulatory peptides. The apparent discrepancy between observed degeneracy in the recognition of single amino acid-substituted Hb peptides and overall Ag specificity of the high-affinity TCRs was examined by generating chimeric peptides between the stimulatory Hb and nonstimulatory moth cytochrome c peptides. These experiments showed that MHC anchor residues significantly affected TCR recognition of peptide. The high-affinity TCRs allowed us to estimate the affinity, in the millimolar range, of immunologically relevant interactions of the TCR with peptide/MHC ligands that were previously unmeasurable because of their weak nature. Thus, through the study of high-affinity TCRs, we demonstrated that a TCR is more tolerant of single TCR contact residue substitutions than other peptide changes, revealing that recognition of Ag by T cells can exhibit both specificity and degeneracy.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Epitopes, T-Lymphocyte,
http://linkedlifedata.com/resource/pubmed/chemical/Hemoglobins,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Antigen, T-Cell
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Nov
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| pubmed:issn |
0022-1767
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
15
|
| pubmed:volume |
177
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
6911-9
|
| pubmed:dateRevised |
2007-12-3
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| pubmed:meshHeading |
pubmed-meshheading:17082606-Amino Acid Substitution,
pubmed-meshheading:17082606-Animals,
pubmed-meshheading:17082606-Antigen Presentation,
pubmed-meshheading:17082606-Cell Adhesion,
pubmed-meshheading:17082606-Cell Line, Tumor,
pubmed-meshheading:17082606-Coculture Techniques,
pubmed-meshheading:17082606-Energy Metabolism,
pubmed-meshheading:17082606-Epitopes, T-Lymphocyte,
pubmed-meshheading:17082606-Hemoglobins,
pubmed-meshheading:17082606-Humans,
pubmed-meshheading:17082606-Hybridomas,
pubmed-meshheading:17082606-Ligands,
pubmed-meshheading:17082606-Major Histocompatibility Complex,
pubmed-meshheading:17082606-Mice,
pubmed-meshheading:17082606-Peptide Fragments,
pubmed-meshheading:17082606-Protein Binding,
pubmed-meshheading:17082606-Receptors, Antigen, T-Cell,
pubmed-meshheading:17082606-T-Lymphocytes
|
| pubmed:year |
2006
|
| pubmed:articleTitle |
The study of high-affinity TCRs reveals duality in T cell recognition of antigen: specificity and degeneracy.
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| pubmed:affiliation |
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
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| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, N.I.H., Extramural
|