| pubmed-article:16287711 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:16287711 | lifeskim:mentions | umls-concept:C0012923 | lld:lifeskim |
| pubmed-article:16287711 | lifeskim:mentions | umls-concept:C0032659 | lld:lifeskim |
| pubmed-article:16287711 | lifeskim:mentions | umls-concept:C1332717 | lld:lifeskim |
| pubmed-article:16287711 | lifeskim:mentions | umls-concept:C1706438 | lld:lifeskim |
| pubmed-article:16287711 | lifeskim:mentions | umls-concept:C0039194 | lld:lifeskim |
| pubmed-article:16287711 | lifeskim:mentions | umls-concept:C1704387 | lld:lifeskim |
| pubmed-article:16287711 | lifeskim:mentions | umls-concept:C0003320 | lld:lifeskim |
| pubmed-article:16287711 | lifeskim:mentions | umls-concept:C1522642 | lld:lifeskim |
| pubmed-article:16287711 | lifeskim:mentions | umls-concept:C0085358 | lld:lifeskim |
| pubmed-article:16287711 | lifeskim:mentions | umls-concept:C0870441 | lld:lifeskim |
| pubmed-article:16287711 | lifeskim:mentions | umls-concept:C1413244 | lld:lifeskim |
| pubmed-article:16287711 | lifeskim:mentions | umls-concept:C2698600 | lld:lifeskim |
| pubmed-article:16287711 | lifeskim:mentions | umls-concept:C0205322 | lld:lifeskim |
| pubmed-article:16287711 | lifeskim:mentions | umls-concept:C0205369 | lld:lifeskim |
| pubmed-article:16287711 | lifeskim:mentions | umls-concept:C0332479 | lld:lifeskim |
| pubmed-article:16287711 | lifeskim:mentions | umls-concept:C1510996 | lld:lifeskim |
| pubmed-article:16287711 | pubmed:issue | 10 | lld:pubmed |
| pubmed-article:16287711 | pubmed:dateCreated | 2005-11-22 | lld:pubmed |
| pubmed-article:16287711 | pubmed:abstractText | The forces that govern clonal selection during the genesis and maintenance of specific T cell responses are complex, but amenable to decryption by interrogation of constituent clonotypes within the antigen-experienced T cell pools. Here, we used point-mutated peptide-major histocompatibility complex class I (pMHCI) antigens, unbiased TCRB gene usage analysis, and polychromatic flow cytometry to probe directly ex vivo the clonal architecture of antigen-specific CD8(+) T cell populations under conditions of persistent exposure to structurally stable virus-derived epitopes. During chronic infection with cytomegalovirus and Epstein-Barr virus, CD8(+) T cell responses to immunodominant viral antigens were oligoclonal, highly skewed, and exhibited diverse clonotypic configurations; TCRB CDR3 sequence analysis indicated positive selection at the protein level. Dominant clonotypes demonstrated high intrinsic antigen avidity, defined strictly as a physical parameter, and were preferentially driven toward terminal differentiation in phenotypically heterogeneous populations. In contrast, subdominant clonotypes were characterized by lower intrinsic avidities and proportionately greater dependency on the pMHCI-CD8 interaction for antigen uptake and functional sensitivity. These findings provide evidence that interclonal competition for antigen operates in human T cell populations, while preferential CD8 coreceptor compensation mitigates this process to maintain clonotypic diversity. Vaccine strategies that reconstruct these biological processes could generate T cell populations that mediate optimal delivery of antiviral effector function. | lld:pubmed |
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| pubmed-article:16287711 | pubmed:language | eng | lld:pubmed |
| pubmed-article:16287711 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16287711 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:16287711 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16287711 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16287711 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16287711 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16287711 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:16287711 | pubmed:month | Nov | lld:pubmed |
| pubmed-article:16287711 | pubmed:issn | 0022-1007 | lld:pubmed |
| pubmed-article:16287711 | pubmed:author | pubmed-author:ConnorsMarkM | lld:pubmed |
| pubmed-article:16287711 | pubmed:author | pubmed-author:BrenchleyJaso... | lld:pubmed |
| pubmed-article:16287711 | pubmed:author | pubmed-author:DouekDaniel... | lld:pubmed |
| pubmed-article:16287711 | pubmed:author | pubmed-author:KoupRichard... | lld:pubmed |
| pubmed-article:16287711 | pubmed:author | pubmed-author:BettsMichael... | lld:pubmed |
| pubmed-article:16287711 | pubmed:author | pubmed-author:HillBrenna... | lld:pubmed |
| pubmed-article:16287711 | pubmed:author | pubmed-author:RoedererMario... | lld:pubmed |
| pubmed-article:16287711 | pubmed:author | pubmed-author:SewellAndrew... | lld:pubmed |
| pubmed-article:16287711 | pubmed:author | pubmed-author:PriceDavid... | lld:pubmed |
| pubmed-article:16287711 | pubmed:author | pubmed-author:WooldridgeLin... | lld:pubmed |
| pubmed-article:16287711 | pubmed:author | pubmed-author:GostickEmmaE | lld:pubmed |
| pubmed-article:16287711 | pubmed:author | pubmed-author:RuffLaura ELE | lld:pubmed |
| pubmed-article:16287711 | pubmed:author | pubmed-author:MiguelesSteve... | lld:pubmed |
| pubmed-article:16287711 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:16287711 | pubmed:day | 21 | lld:pubmed |
