原始出处：Nature Medicine，doi:10.1038/nm.1779，Andrew K Sewell，James L Riley
Control of HIV-1 immune escape by CD8 T cells expressing enhanced T-cell receptor
Angel Varela-Rohena1, Peter E Molloy2, Steven M Dunn2, Yi Li2, Megan M Suhoski1, Richard G Carroll1, Anita Milicic3, Tara Mahon2, Deborah H Sutton2, Bruno Laugel3, Ruth Moysey2, Brian J Cameron2, Annelise Vuidepot2, Marco A Purbhoo2, David K Cole4, Rodney E Phillips3, Carl H June1, Bent K Jakobsen5, Andrew K Sewell3,4,6 & James L Riley1,6
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.