Efficiency of T-cell receptor expression in dual-specific T cells is controlled by the intrinsic qualities of the TCR chains within the TCR-CD3 complex
Efficiency of T-cell receptor expression in dual-specific T cells is controlled by the intrinsic qualities of the TCR chains within the TCR-CD3 complex
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DOI：
10.1182/blood-2006-03-013318
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发表时间：
2007-01-01
期刊：
影响因子：
20.3
通讯作者：
Falkenburg, J. H. Frederik
中科院分区：
文献类型：
--
作者：
Heemskerk, Mirjam H. M.;Hagedoorn, Renate S.;Falkenburg, J. H. Frederik
T淋巴细胞的基因工程是一种有吸引力的策略，可以专门将T细胞免疫重新定向到病毒感染和恶性肿瘤。我们先前通过转移次要组织相容抗原HA-2特异性T细胞受体(TCR)证明了巨细胞病毒(CMV)特异性T细胞的重定向抗白血病活性。HA-2-TCR转导的巨细胞病毒特异性T细胞对HA-2表达的白血病细胞和CM表达的细胞都是有效的效应者。这些T细胞的功能活性与TCR细胞表面的表达有关。在本研究中，我们分析了转移的和内源性的TCRs的哪些特性对有效的细胞表面表达至关重要。我们证明了导入的TCR的表达不是一个随机过程，而是由导入的和内源性表达的TCR的特性决定的。TCR复合体的固有性质决定了TCR细胞表面表达的效率。此外，我们证明了嵌合TCR是可以形成的，并且TCR的表达效率与TCR是逆转录病毒导入还是自然表达无关。总之，引入的、内源性的和嵌合的TCR竞争细胞表面的表达，有利于具有最佳配对特性的TCR-CD3复合体。(C)美国血液病学会2007年
Genetic engineering of T lymphocytes is an attractive strategy to specifically redirect T-cell immunity toward viral infections and malignancies. We previously demonstrated redirected antileukemic reactivity of cytomegalovirus (CMV)-specific T cells by transfer of minor histocompatibility antigen HA-2-specific T-cell receptors (TCRs). HA-2-TCR-transferred CMV-specific T cells were potent effectors against HA-2-expressing leukemic cells, as well as CM-expressing cells. Functional activity of these T cells correlated with TCR cell-surface expression. In the present study we analyzed which properties of transferred and endogenous TCRs are crucial for efficient cell-surface expression. We demonstrate that expression of the introduced TCR is not a random process but is determined by characteristics of both the introduced and the endogenously expressed TCR. The efficiency of TCR cell-surface expression is controlled by the intrinsic quality of the TCR complex. In addition, we demonstrate that chimeric TCRs can be formed and that efficiency of TCR expression is independent of whether TCRs are retrovirally introduced or naturally expressed. In conclusion, introduced, endogenous, and chimeric TCRs compete for cell-surface expression in favor of the TCR-CD3 complex with best-pairing properties. (c) 2007 by The American Society of Hematology