POSITIVE AND NEGATIVE SELECTION OF AN ANTIGEN RECEPTOR ON T-CELLS IN TRANSGENIC MICE
POSITIVE AND NEGATIVE SELECTION OF AN ANTIGEN RECEPTOR ON T-CELLS IN TRANSGENIC MICE
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DOI：
10.1038/336073a0
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发表时间：
1988-11-03
期刊：
影响因子：
64.8
通讯作者：
LOH, DY
中科院分区：
文献类型：
--
作者：
SHA, WC;NELSON, CA;LOH, DY
外周中发现的T细胞库被认为是由胸腺中涉及T淋巴细胞抗原受体的两个发育事件形成的。首先，T细胞和主要组织相容性复合体（MHC）分子之间的相互作用选择了一个T细胞库，倾向于在自身MHC分子的背景下识别抗原1 -5。此外，对自身MHC分子反应强烈的T细胞通过称为自身耐受性的过程被消除6 -10。我们最近描述了表达来自细胞毒性T淋巴细胞2C的αβ T细胞受体的转基因小鼠（参考文献11）。克隆2C来源于BALB.B（H-2 B）抗BALB/c（H-2 d）混合淋巴细胞培养物，对Ld I类MHC抗原具有特异性。在转基因H-2b小鼠中，外周的大部分T细胞表达2C T细胞受体。这些T细胞主要是CD 4-CD 8+，并且能够特异性地裂解携带Ld的靶细胞。我们现在报告，在转基因小鼠表达Ld的外周，功能性T细胞轴承2C T细胞受体被删除。这种自身反应性T细胞的消除似乎发生在胸腺细胞发育的CD 4 + CD 8+阶段或之前。此外，我们报告在H-28小鼠，一个非自身反应性的目标单倍型，大量的CDS*T细胞携带的2C T细胞受体没有被发现，提供了强有力的证据，2C T细胞受体特异性的H-2b分子的积极选择。
The T-cell repertoire found in the periphery is thought to be shaped by two developmental events in the thymus that involve the antigen receptors of T lymphocytes. First, interactions between T cells and major histocompatibility complex (MHC) molecules select a T-cell repertoire skewed towards recognition of antigens in the context of self-MHC molecules1–5. In addition, T cells that react strongly to self-MHC molecules are eliminated by a process called self-tolerance6–10. We have recently described transgenic mice expressing theαβT-cell receptor from the cytotoxic T lymphocyte 2C (ref. 11). The clone 2C was derived from a BALB.B (H–2b) anti-BALB/c (H–2d) mixed lymphocyte culture and is specific for the Ldclass I MHC antigen. In transgenic H–2bmice, a large fraction of T cells in the periphery expressed the 2C T-cell receptor. These T cells were predominantly CD4-CD8+and were able to specifically lyse target cells bearing Ld. We now report that in the periphery of transgenic mice expressing Ld, functional T cells bearing the 2C T-cell receptor were deleted. This elimination of autoreactive T cells appears to take place at or before the CD4+CD8+stage in thymocyte development. In addition, we report that in H–28mice, a non-autoreactive target haplotype, large numbers of CDS*T cells bearing the 2C T-cell receptor were not found, providing strong evidence for the positive selection of the 2C T-cell receptor specificity by H–2bmolecules.