Leitman Ellen M, Palmer Christine D, Buus Søren, Chen Fabian, Riddell Lynn, Sims Stuart, Klenerman Paul, Sáez-Cirión Asier, Walker Bruce D, Hess Paul R, Altfeld Marcus, Matthews Philippa C, Goulder Philip J R
Department of Paediatrics, University of Oxford, Oxford, United Kingdom.
Harvard Medical School, Boston, Massachusetts, United States of America.
PLoS One. 2017 Oct 11;12(10):e0184496. doi: 10.1371/journal.pone.0184496. eCollection 2017.
Antigen-specific T-cells are highly variable, spanning potent antiviral efficacy and damaging auto-reactivity. In virus infections, identifying the most efficacious responses is critical to vaccine design. However, current methods depend on indirect measures or on ex vivo expanded CTL clones. We here describe a novel application of cytotoxic saporin-conjugated tetramers to kill antigen-specific T-cells without significant off-target effects. The relative efficacy of distinct antiviral CD8+ T-cell specificity can be directly assessed via antigen-specific CD8+ T-cell depletion. The utility of these reagents is demonstrated here in identifying the CD8+ T-cell specificity most effective in preventing HIV progression in HIV-infected HLA-B*27-positive immune controllers.
抗原特异性T细胞具有高度变异性，涵盖强大的抗病毒功效和有害的自身反应性。在病毒感染中，识别最有效的反应对于疫苗设计至关重要。然而，目前的方法依赖于间接测量或体外扩增的CTL克隆。我们在此描述了一种细胞毒性皂草素偶联四聚体的新应用，可杀死抗原特异性T细胞而无明显的脱靶效应。通过抗原特异性CD8 + T细胞耗竭可直接评估不同抗病毒CD8 + T细胞特异性的相对功效。本文展示了这些试剂在识别对预防HIV感染的HLA - B * 27阳性免疫控制者中HIV进展最有效的CD8 + T细胞特异性方面的效用。
