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- Title
Control of HIV-1 immune escape by CD8 T cells expressing enhanced T-cell receptor.
- Authors
Varela-Rohena, Angel; Molloy, Peter E; Dunn, Steven M; Li, Yi; Suhoski, Megan M; Carroll, Richard G; Milicic, Anita; Mahon, Tara; Sutton, Deborah H; Laugel, Bruno; Moysey, Ruth; Cameron, Brian J; Vuidepot, Annelise; Purbhoo, Marco A; Cole, David K; Phillips, Rodney E; June, Carl H; Jakobsen, Bent K; Sewell, Andrew K; Riley, James L
- Abstract
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.
- Publication
Nature medicine, 2008, Vol 14, Issue 12, p1390
- ISSN
1546-170X
- Publication type
Journal Article
- DOI
10.1038/nm.1779