Brändle D, Müller C, Rülicke T, Hengartner H, Pircher H
Institute of Experimental Immunology, University of Zurich, Switzerland.
Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9529-33. doi: 10.1073/pnas.89.20.9529.
We have examined the expression of the recombination activating gene RAG-1 by in situ hybridization to thymi from mice bearing transgenes for the T-cell receptor (TCR) alpha chain, TCR beta chain, or both TCR alpha and beta chains. RAG-1 transcription was found in the thymic cortex of transgenic mice carrying a single TCR alpha- or TCR beta-chain transgene, comparable to normal mice. However, RAG-1 transcription was strikingly reduced in the thymic cortex from transgenic mice carrying both TCR alpha- and beta-chain genes and expressing major histocompatibility complex (MHC) class I (H-2b) molecules necessary for positive selection of the transgenic TCR. In contrast, thymi of transgenic mice also carrying both TCR alpha- and beta-chain genes but expressing MHC molecules (H-2d) that did not positively select the transgenic TCR displayed high levels of RAG-1 transcription. The low thymic RAG-1 expression coincided with high transgenic TCR alpha-chain surface expression and with inhibition of endogenous TCR alpha-chain rearrangement. Our findings suggest that binding of the TCR to self MHC molecules during positive selection down-regulates RAG-1 transcription in cortical thymocytes and thereby prevents further TCR alpha-chain rearrangements.
我们通过原位杂交技术，检测了携带T细胞受体（TCR）α链、TCRβ链或同时携带TCRα链和β链转基因的小鼠胸腺中重组激活基因RAG-1的表达情况。在携带单个TCRα链或TCRβ链转基因的转基因小鼠胸腺皮质中发现了RAG-1转录，与正常小鼠相当。然而，在同时携带TCRα链和β链基因并表达转基因TCR阳性选择所需的主要组织相容性复合体（MHC）I类（H-2b）分子的转基因小鼠胸腺皮质中，RAG-1转录显著降低。相反，同时携带TCRα链和β链基因但表达不能对转基因TCR进行阳性选择的MHC分子（H-2d）的转基因小鼠胸腺，显示出高水平的RAG-1转录。胸腺中RAG-1低表达与转基因TCRα链高表面表达以及内源性TCRα链重排的抑制相吻合。我们的研究结果表明，在阳性选择过程中，TCR与自身MHC分子的结合会下调皮质胸腺细胞中RAG-1的转录，从而阻止进一步的TCRα链重排。
