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

Journal article

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.

Authors: Varela-Rohena, A; Molloy, P; Dunn, S; Li, Y; Suhoski, M

• Publication status: Published
• Journal: Nature medicine
• Volume: 14
• Issue: 12
• Pages: 1390-1395
• Publication date: 2008-12-01
• DOI: 10.1038/nm.1779
• EISSN: 1546-170X
• ISSN: 1078-8956
• Language: English
• Keywords: Gene Products, gag; CD8-Positive T-Lymphocytes; Peptide Fragments; Protein Binding; Receptors, Antigen, T-Cell; HIV-1; Amino Acid Sequence; Cells, Cultured; Mutation; Solubility; Humans