期刊
MOLECULAR IMMUNOLOGY
卷 47, 期 7-8, 页码 1613-1618出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.molimm.2010.01.012
关键词
T cell; T cell receptor; Transgenic mice
资金
- Medical Research Council, UK
- BBSRC [BB/F020732/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/F020732/1] Funding Source: researchfish
T cell receptor transfer is an attractive strategy for the generation of antigen specific T cells to target infection and malignancy. Cross pairing of the transduced and endogenous TCR chains produces new and potentially auto-reactive specificities and dilutes the therapeutic TCR. This is further complicated as the efficiency of pairing for each alpha beta pair is unpredictable and the factors which influence it are not well characterized. Complementarity determining region 3 (CDR3) loops are the main sources of TCR alpha and beta diversity due to nucleotide insertion and deletion at V(D)J junctions. Given the variability in composition and length of these non-germ line encoded structures, it is likely that structural strain may occur during formation of some TCR hetero-dimers contributing to the observed pairing restrictions. The beta chain of the HY specific T cell receptor C6 is such an example. Despite pairing efficiently with the C6 alpha chain, it pairs poorly with many other alpha chains. To investigate whether the long, C6 beta CDR3 region underlies this effect, it was replaced with a short, artificial CDR3 region that restored efficient pairing with the endogenous alpha chain repertoire. Molecular modelling is consistent with the beta chain CDR3 region causing steric incompatibility. Despite poor pairing and low surface expression, the WT C6 beta chain mediates positive selection in retrogenic mice. (C) 2010 Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据