通過基因改革工程，研究人員讓“殺手”T細(xì)胞更好地限制了HIV在培養(yǎng)液中的擴(kuò)散,。他們在日前在線出版的《自然—醫(yī)學(xué)》期刊中說,，這種能力升高的T細(xì)胞還能識別已經(jīng)發(fā)生變異并試圖逃過免疫反應(yīng)的病毒。
T細(xì)胞受體（TCR）能夠識別病毒蛋白質(zhì)碎片,，并在受感染細(xì)胞表面發(fā)出警告信息,，T細(xì)胞因此得知了HIV的出現(xiàn)。目前,，分離這種能夠識別HIV的特別T細(xì)胞的方法主要基于克隆取自HIV患者的細(xì)胞,，這是一個緩慢而費力的過程，而且,，這些細(xì)胞中的TCR鑒別受感染細(xì)胞的能力很弱,。病毒能夠通過變異而逃脫探測。
James Riley和同事利用噬菌體表面展示技術(shù)，從取自HIV患者的T細(xì)胞分離出TCR,，這種TCR能很好地鑒別出HIV的存在,。然后，他們通過基因工程改造這種TCR,，讓它能更好地探尋病毒,。將這種TCR置入T細(xì)胞中，結(jié)果產(chǎn)生出力量更大的“殺手”細(xì)胞,，能夠在培養(yǎng)液中更好地限制HIV的擴(kuò)散,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
