Selection of antigen-specific T cells by a single IEk peptide combination.
Selection of antigen-specific T cells by a single IEk peptide combination.
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DOI：
10.1084/jem.186.9.1441
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发表时间：
1997-11-03
期刊：
影响因子：
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通讯作者：
Marrack P
中科院分区：
文献类型：
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作者：
Liu CP;Parker D;Kappler J;Marrack P
在正常小鼠中，主要组织相容性复合体（MHC）蛋白质与许多不同的肽结合，这些肽来源于其宿主的蛋白质。在胸腺中，这种MHC +肽配体集合的多样性允许携带许多不同T细胞受体（TCR）的胸腺细胞通过MHC +肽配体和胸腺细胞TCR之间的低亲合力反应而成熟。为了研究这个问题，研究了对充分研究的MHC +肽，IEk +蛾细胞色素c 88-103（MCC）的组合特异性的T细胞的选择。产生表达与单个肽结合的IEk的小鼠，所述单个肽是MCC的变体，其中关键TCR接触残基99 K改变为A，或者是小鼠血红蛋白64-76（Hb）肽72 A的变体。IEk与MCC变体的结合导致了一些对IEk + MCC配体特异性的T细胞的克隆缺失;然而，它也积极选择了许多可以与该配体反应的T细胞。所选择的T细胞上的一些TCR与来自正常小鼠的细胞上的TCR相关，而一些则不相关。另一方面，与Hb变体结合的IEk没有选择任何可以与IEk + MCC反应的T细胞。这些结果表明，虽然正选择是一个部分简并事件，参与正选择的肽序列控制所选择的库。
In normal mice, major histocompatibility complex (MHC) proteins are bound to many different peptides, derived from the proteins of their host. In the thymus, the diversity of this collection of MHC + peptide ligands allows thymocytes bearing many different T cell receptors (TCRs) to mature by low avidity reactions between the MHC + peptide ligands and the thymocyte TCRs. To investigate this problem, the selection of T cells specific for a well-studied combination of MHC + peptide, IEk + moth cytochrome c 88–103 (MCC), was investigated. Mice were created that expressed IEk bound to a single peptide, either a variant of MCC in which a critical TCR contact residue, 99K, was changed to A, or a variant of a mouse hemoglobin 64–76 (Hb) peptide, 72A. IEk bound to the MCC variant caused the clonal deletion of some T cells specific for the IEk + MCC ligand; nevertheless, it also positively selected many T cells that could react with this ligand. Some of the TCRs on the selected T cells were related to those on cells from normal mice and some were not. IEk bound to the Hb variant, on the other hand, did not select any T cells which could react with IEk + MCC. These results demonstrate that although positive selection is a partially degenerate event, the sequence of the peptide involved in positive selection controls the selected repertoire.