Control of HIV-1 immune escape by CD8 T cells expressing enhanced T-cell receptor

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 ORCID: https://orcid.org/0000-0003-0028-9396, Phillips, Rodney E., June, Carl H., Jakobsen, Bent K., Sewell, Andrew K. ORCID: https://orcid.org/0000-0003-3194-3135 and Riley, James L. 2008. Control of HIV-1 immune escape by CD8 T cells expressing enhanced T-cell receptor. Nature Medicine 14 (12) , pp. 1390-1395. 10.1038/nm.1779

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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 (KD < 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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI)
Subjects:	Q Science > QR Microbiology > QR180 Immunology
Publisher:	Nature Publishing Group
ISSN:	1078-8956
Last Modified:	20 Oct 2022 08:59
URI:	https://orca.cardiff.ac.uk/id/eprint/30298

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