Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute; and 2 Program in Cellular and Molecular Medicine, Children's Hospital, and Immune Disease Institute, Harvard Medical School, Boston, MA 02115.
J Exp Med. 2013 Sep 23;210(10):1911-8. doi: 10.1084/jem.20130876. Epub 2013 Aug 26.
Antigen receptor editing-a process of secondary rearrangements of antigen receptor genes in autoreactive lymphocytes-is a well-established tolerance mechanism in B cells, whereas its role in T cells remains controversial. Here, we investigated this issue using a novel Tcra knock-in locus, which ensured appropriate timing of TCRα expression and allowed secondary rearrangements. Under these conditions the only response to self-antigen that could be unambiguously identified was negative selection of CD4/CD8 double positive thymocytes. No evidence could be obtained for antigen-induced TCR editing, whereas replacement of the transgenic TCRα chain by ongoing gene rearrangement occurred in some cells irrespective of the presence or absence of self-antigen.
抗原受体编辑——自身反应性淋巴细胞中抗原受体基因的二次重排过程——是 B 细胞中一种成熟的耐受机制，而其在 T 细胞中的作用仍存在争议。在这里，我们使用一种新型的 Tcra 基因敲入（knock-in）位点来研究这个问题，该位点确保了 TCRα 表达的适当时间，并允许二次重排。在这些条件下，唯一可以明确识别的对自身抗原的反应是 CD4/CD8 双阳性胸腺细胞的阴性选择。没有证据表明存在抗原诱导的 TCR 编辑，而转基因 TCRα 链的替换由持续的基因重排发生在一些细胞中，无论是否存在自身抗原。
