rdf:type |
|
lifeskim:mentions |
umls-concept:C0019704,
umls-concept:C0034790,
umls-concept:C0039194,
umls-concept:C0085358,
umls-concept:C0439662,
umls-concept:C0870509,
umls-concept:C1332717,
umls-concept:C1413244,
umls-concept:C1706438,
umls-concept:C2349975,
umls-concept:C2587213,
umls-concept:C2698600
|
pubmed:issue |
12
|
pubmed:dateCreated |
2008-12-5
|
pubmed:abstractText |
HIV's considerable capacity to vary its HLA-I-restricted peptide antigens allows it to escape from host cytotoxic T lymphocytes (CTLs). Nevertheless, therapeutics able to target HLA-I-associated antigens, with specificity for the spectrum of preferred CTL escape mutants, could prove effective. Here we use phage display to isolate and enhance a T-cell antigen receptor (TCR) originating from a CTL line derived from an infected person and specific for the immunodominant HLA-A(*)02-restricted, HIVgag-specific peptide SLYNTVATL (SL9). High-affinity (K(D) < 400 pM) TCRs were produced that bound with a half-life in excess of 2.5 h, retained specificity, targeted HIV-infected cells and recognized all common escape variants of this epitope. CD8 T cells transduced with this supraphysiologic TCR produced a greater range of soluble factors and more interleukin-2 than those transduced with natural SL9-specific TCR, and they effectively controlled wild-type and mutant strains of HIV at effector-to-target ratios that could be achieved by T-cell therapy.
|
pubmed:grant |
|
pubmed:language |
eng
|
pubmed:journal |
|
pubmed:citationSubset |
IM
|
pubmed:chemical |
|
pubmed:status |
MEDLINE
|
pubmed:month |
Dec
|
pubmed:issn |
1546-170X
|
pubmed:author |
pubmed-author:CameronBrian JBJ,
pubmed-author:CarrollRichard GRG,
pubmed-author:ColeDavid KDK,
pubmed-author:DunnSteven MSM,
pubmed-author:JakobsenBent KBK,
pubmed-author:JuneCarl HCH,
pubmed-author:LaugelBrunoB,
pubmed-author:LiYiY,
pubmed-author:MahonTaraT,
pubmed-author:MilicicAnitaA,
pubmed-author:MolloyPeter EPE,
pubmed-author:MoyseyRuthR,
pubmed-author:PhillipsRodney ERE,
pubmed-author:PurbhooMarco AMA,
pubmed-author:RileyJames LJL,
pubmed-author:SewellAndrew KAK,
pubmed-author:SuhoskiMegan MMM,
pubmed-author:SuttonDeborah HDH,
pubmed-author:Varela-RohenaAngelA,
pubmed-author:VuidepotAnneliseA
|
pubmed:issnType |
Electronic
|
pubmed:volume |
14
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
1390-5
|
pubmed:dateRevised |
2011-9-26
|
pubmed:meshHeading |
pubmed-meshheading:18997777-Amino Acid Sequence,
pubmed-meshheading:18997777-CD8-Positive T-Lymphocytes,
pubmed-meshheading:18997777-Cells, Cultured,
pubmed-meshheading:18997777-Gene Products, gag,
pubmed-meshheading:18997777-HIV-1,
pubmed-meshheading:18997777-Humans,
pubmed-meshheading:18997777-Mutation,
pubmed-meshheading:18997777-Peptide Fragments,
pubmed-meshheading:18997777-Protein Binding,
pubmed-meshheading:18997777-Receptors, Antigen, T-Cell,
pubmed-meshheading:18997777-Solubility
|
pubmed:year |
2008
|
pubmed:articleTitle |
Control of HIV-1 immune escape by CD8 T cells expressing enhanced T-cell receptor.
|
pubmed:affiliation |
Department of Pathology and Laboratory Medicine, Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6160, USA.
|
pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
|