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胸腺自身肽的特异性识别诱导细胞毒性T淋巴细胞的阳性选择。

Specific recognition of thymic self-peptides induces the positive selection of cytotoxic T lymphocytes.

作者信息

Hu Q, Bazemore Walker C R, Girao C, Opferman J T, Sun J, Shabanowitz J, Hunt D F, Ashton-Rickardt P G

机构信息

Gwen Knapp Center for Lupus and Immunology Research, Department of Pathology, University of Chicago, Illinois 60637, USA.

出版信息

Immunity. 1997 Aug;7(2):221-31. doi: 10.1016/s1074-7613(00)80525-7.

DOI:10.1016/s1074-7613(00)80525-7
PMID:9285407
Abstract

To understand how thymic selection gives rise to T cells that are capable of major histocompatibility complex (MHC)-restricted recognition of antigen but are tolerant of self, we directly examined how peptide/MHC ligands expressed on thymic epithelial cells trigger the positive selection of immature thymocytes. We demonstrate that abundant self-peptides, purified from the H-2D(b) molecules of thymic epithelial cells, are specifically recognized during the positive selection of CD8+ T cells, implying that positive selection generates a repertoire of T cells that is weakly self-reactive. We also found that this recognition is somewhat cross-reactive, thereby providing an explanation for how the specific recognition of a limited repertoire of thymic self-peptides can select a diverse repertoire of T cells.

摘要

为了理解胸腺选择如何产生能够对主要组织相容性复合体(MHC)限制的抗原进行识别但对自身耐受的T细胞,我们直接研究了胸腺上皮细胞上表达的肽/MHC配体如何触发未成熟胸腺细胞的阳性选择。我们证明,从胸腺上皮细胞的H-2D(b)分子中纯化的大量自身肽在CD8+T细胞的阳性选择过程中被特异性识别,这意味着阳性选择产生了一组弱自身反应性的T细胞库。我们还发现这种识别具有一定的交叉反应性,从而解释了对有限的胸腺自身肽库的特异性识别如何能够选择多样化的T细胞库。

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1
Specific recognition of thymic self-peptides induces the positive selection of cytotoxic T lymphocytes.胸腺自身肽的特异性识别诱导细胞毒性T淋巴细胞的阳性选择。
Immunity. 1997 Aug;7(2):221-31. doi: 10.1016/s1074-7613(00)80525-7.
2
Affinity of thymic self-peptides for the TCR determines the selection of CD8(+) T lymphocytes in the thymus.胸腺自身肽与T细胞受体的亲和力决定了胸腺中CD8(+) T淋巴细胞的选择。
Int Immunol. 2000 Sep;12(9):1353-63. doi: 10.1093/intimm/12.9.1353.
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A role for accessibility to self-peptide-self-MHC complexes in intrathymic negative selection.自身肽-自身MHC复合物的可及性在胸腺内阴性选择中的作用。
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CD8+ T lymphocytes in double alpha beta TCR transgenic mice. I. TCR expression and thymus selection in the absence or in the presence of self-antigen.双αβTCR转基因小鼠中的CD8 + T淋巴细胞。I. 在不存在或存在自身抗原的情况下TCR表达和胸腺选择。
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In vitro positive selection of alpha beta TCR transgenic thymocytes by a conditionally immortalized cortical epithelial clone.通过条件永生化的皮质上皮克隆对αβTCR转基因胸腺细胞进行体外阳性选择。
Int Immunol. 1997 Mar;9(3):381-93. doi: 10.1093/intimm/9.3.381.
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Thymic selection and peripheral activation of CD8 T cells by the same class I MHC/peptide complex.同一I类主要组织相容性复合体/肽复合物对CD8 T细胞的胸腺选择和外周激活。
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CD8 expression up to the double-positive CD3(low/intermediate) stage of thymic differentiation is sufficient for development of peripheral functional cytotoxic T lymphocytes.在胸腺分化的双阳性CD3(低/中等)阶段之前的CD8表达,对于外周功能性细胞毒性T淋巴细胞的发育而言已足够。
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Alpha beta TCRs differ in the degree of their specificity for the positively selecting MHC/peptide ligand.αβT细胞受体对阳性选择的MHC/肽配体的特异性程度有所不同。
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T cell receptor antagonist peptides induce positive selection.T细胞受体拮抗剂肽诱导阳性选择。
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The interferon regulatory transcription factor IRF-1 controls positive and negative selection of CD8+ thymocytes.干扰素调节转录因子IRF-1控制CD8+胸腺细胞的阳性和阴性选择。
Immunity. 1997 Aug;7(2):243-54. doi: 10.1016/s1074-7613(00)80527-0.

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Nat Immunol. 2012 Jan 19;13(2):121-8. doi: 10.1038/ni.2190.
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