A T cell receptor-specific blockade of positive selection.

A T cell receptor-specific blockade of positive selection.
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DOI:
10.1084/jem.189.1.13
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发表时间:
1999-01-04
影响因子:
15.3
通讯作者:
Davis, M M
Davis, M M
中科院分区:
医学1区
文献类型:
--
作者:
Baldwin, K K;Reay, P A;Wu, L;Farr, A;Davis, M M

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为了研究内源肽对胸腺细胞选择过程中发生的发育过程的影响,我们使用了单克隆抗体,当主要组织相容性复合体 (MHC) 分子 I-Ek 与蛾细胞色素 c 肽结合时,该抗体优先识别该分子 (88-103)。其中一种抗体 (G35) 特异性阻断表达 T 细胞受体的转基因胸腺细胞的阳性选择,该受体对该肽-MHC 复合物有反应。此外,G35 不会阻碍携带不同 I-Ek-肽复合物受体的转基因 T 细胞的分化。该抗体可识别在大部分胸腺抗原呈递细胞(包括皮质和髓质上皮细胞)上发现的内源 I-Ek-肽复合物的子集。 G35 对肽序列微小改变的敏感性表明,介导特定 II 类 MHC 限制性胸腺细胞正向选择的胸腺肽-MHC 复合物在结构上与可在外周激活该胸腺细胞的复合物相关。
To investigate the influence of endogenous peptides on the developmental processes that occur during thymocyte selection, we have used monoclonal antibodies that preferentially recognize the major histocompatibility complex (MHC) molecule I-Ek when it is bound to the moth cytochrome c peptide (88–103). One of these antibodies (G35) specifically blocks the positive selection of transgenic thymocytes expressing a T cell receptor that is reactive to this peptide– MHC complex. Furthermore, G35 does not block the differentiation of transgenic T cells bearing receptors for a different I-Ek–peptide complex. This antibody recognizes a subset of endogenous I-Ek–peptide complexes found on a significant fraction of thymic antigen-presenting cells, including cortical and medullary epithelial cells. The sensitivity of G35 to minor alterations in peptide sequence suggests that the thymic peptide–MHC complexes that mediate the positive selection of a particular class II MHC–restricted thymocyte are structurally related to the complexes that can activate it in the periphery.