通过基因改革工程，研究人员让“杀手”T细胞更好地限制了HIV在培养液中的扩散。他们在日前在线出版的《自然—医学》期刊中说，这种能力升高的T细胞还能识别已经发生变异并试图逃过免疫反应的病毒。
T细胞受体（TCR）能够识别病毒蛋白质碎片，并在受感染细胞表面发出警告信息，T细胞因此得知了HIV的出现。目前，分离这种能够识别HIV的特别T细胞的方法主要基于克隆取自HIV患者的细胞，这是一个缓慢而费力的过程，而且，这些细胞中的TCR鉴别受感染细胞的能力很弱。病毒能够通过变异而逃脱探测。
James Riley和同事利用噬菌体表面展示技术，从取自HIV患者的T细胞分离出TCR，这种TCR能很好地鉴别出HIV的存在。然后，他们通过基因工程改造这种TCR，让它能更好地探寻病毒。将这种TCR置入T细胞中，结果产生出力量更大的“杀手”细胞，能够在培养液中更好地限制HIV的扩散。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature Medicine，doi:10.1038/nm.1779，Bent K Jakobsen，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
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.
1 Abramson Family Cancer Research Institute and Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 556 BRB II/III, 421 Curie Boulevard, Philadelphia, Pennsylvania 19104-6160, USA.
2 Immunocore Ltd., 57c Milton Park, Abingdon, Oxon OX14 4RX, UK.
3 The Peter Medawar Building for Pathogen Research, University of Oxford, South Parks Road, Oxford OX1 3SY, UK.
4 Department of Medical Biochemistry and Immunology, Henry Wellcome Building, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK.
5 Adaptimmune Ltd., 57c Milton Park, Abingdon, Oxon OX14 4RX, UK.
6 These authors contributed equally to this work.
