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在表达TCRβ转基因的重症联合免疫缺陷小鼠中,发育不同的T细胞群体上结构不同的T细胞受体复合物。

Structurally distinct T cell receptor complexes on developmentally distinct T cell populations in severe combined immunodeficiency mice expressing a TCR beta transgene.

作者信息

Shores E W, Nakayama T, Wiest D L, Takahama Y, Sharrow S, Singer A

机构信息

Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.

出版信息

J Immunol. 1993 Feb 15;150(4):1263-75.

PMID:8094405
Abstract

T cell differentiation and TCR expression were assessed in severe combined immunodeficiency (SCID) mice possessing an already rearranged TCRV beta 8 transgene. Unlike nontransgenic SCID mice, TCRV beta 8-transgenic SCID mice contained a broad spectrum of T cell populations, including both immature thymocytes and mature T cells. In TCRV beta 8-transgenic SCID mice, immature CD4-CD8- and CD4+CD8+ thymocytes expressed surface TCR complexes structurally distinct from those expressed by mature single-positive T cells. Immature CD4+CD8+ thymocytes expressed surface TCR beta chains without a clonotypic TCR partner chain and largely without associated CD3 components. In contrast, mature single-positive T cells expressed fully assembled surface TCR complexes containing disulfide-linked heterodimers consisting of transgenic TCR beta chains and endogenous TCR alpha chains. The surface TCR complexes on mature T cells were associated with CD3 components and were competent to transduce TCR-mediated proliferative signals. Thus, T cells at different stages of development in TCRV beta 8-transgenic SCID mice express structurally distinct surface TCR complexes, demonstrating that the developmental stage achieved by T cells in these mice is related to the structure of the surface TCR complexes they express. Indeed, the present results indicate that successful differentiation into single-positive T cells requires surface expression of fully assembled TCR complexes.

摘要

在已重排TCRVβ8转基因的重症联合免疫缺陷(SCID)小鼠中评估T细胞分化和TCR表达。与非转基因SCID小鼠不同,TCRVβ8转基因SCID小鼠含有广泛的T细胞群体,包括未成熟胸腺细胞和成熟T细胞。在TCRVβ8转基因SCID小鼠中,未成熟的CD4-CD8-和CD4+CD8+胸腺细胞表达的表面TCR复合物在结构上与成熟单阳性T细胞表达的不同。未成熟的CD4+CD8+胸腺细胞表达表面TCRβ链,但没有克隆型TCR伙伴链,且大部分没有相关的CD3成分。相比之下,成熟单阳性T细胞表达完全组装的表面TCR复合物,其包含由转基因TCRβ链和内源性TCRα链组成的二硫键连接的异二聚体。成熟T细胞上的表面TCR复合物与CD3成分相关,并能够转导TCR介导的增殖信号。因此,TCRVβ8转基因SCID小鼠中不同发育阶段的T细胞表达结构不同的表面TCR复合物,表明这些小鼠中T细胞达到的发育阶段与其表达的表面TCR复合物的结构有关。事实上,目前的结果表明,成功分化为单阳性T细胞需要完全组装的TCR复合物的表面表达。

相似文献

1
Structurally distinct T cell receptor complexes on developmentally distinct T cell populations in severe combined immunodeficiency mice expressing a TCR beta transgene.在表达TCRβ转基因的重症联合免疫缺陷小鼠中,发育不同的T细胞群体上结构不同的T细胞受体复合物。
J Immunol. 1993 Feb 15;150(4):1263-75.
2
Expression of an unusual T cell receptor (TCR)-V beta repertoire by Ly-6C+ subpopulations of CD4+ and/or CD8+ thymocytes. Evidence for a developmental relationship between Ly-6C+ thymocytes and CD4-CD8-TCR-alpha beta+ thymocytes.CD4⁺和/或CD8⁺胸腺细胞的Ly-6C⁺亚群表达异常的T细胞受体(TCR)-Vβ谱系。Ly-6C⁺胸腺细胞与CD4⁻CD8⁻TCR-αβ⁺胸腺细胞之间存在发育关系的证据。
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T cell receptor-negative thymocytes from SCID mice can be induced to enter the CD4/CD8 differentiation pathway.来自严重联合免疫缺陷(SCID)小鼠的T细胞受体阴性胸腺细胞可被诱导进入CD4/CD8分化途径。
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Receptor-specific allelic exclusion of TCRV alpha-chains during development.发育过程中TCRVα链的受体特异性等位基因排斥
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引用本文的文献

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Irradiation promotes V(D)J joining and RAG-dependent neoplastic transformation in SCID T-cell precursors.辐射促进重症联合免疫缺陷(SCID)T细胞前体中的V(D)J连接和RAG依赖性肿瘤转化。
Mol Cell Biol. 2001 Jan;21(2):400-13. doi: 10.1128/MCB.21.2.400-413.2001.
2
T cell development in mice lacking the CD3-zeta/eta gene.缺乏CD3-ζ/η基因的小鼠中的T细胞发育
EMBO J. 1993 Nov;12(11):4347-55. doi: 10.1002/j.1460-2075.1993.tb06119.x.
3
Stoichiometry of the T cell antigen receptor (TCR) complex: each TCR/CD3 complex contains one TCR alpha, one TCR beta, and two CD3 epsilon chains.
T细胞抗原受体(TCR)复合物的化学计量:每个TCR/CD3复合物包含一条TCRα链、一条TCRβ链和两条CD3ε链。
J Exp Med. 1994 Aug 1;180(2):587-93. doi: 10.1084/jem.180.2.587.
4
Nuclear factors that mediate intrathymic signals are developmentally regulated.介导胸腺内信号的核因子受到发育调控。
J Exp Med. 1994 Dec 1;180(6):2321-7. doi: 10.1084/jem.180.6.2321.
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Developmentally regulated expression of CD3 components independent of clonotypic T cell antigen receptor complexes on immature thymocytes.未成熟胸腺细胞上CD3成分的发育调控性表达独立于克隆型T细胞抗原受体复合物。
J Exp Med. 1994 Oct 1;180(4):1375-82. doi: 10.1084/jem.180.4.1375.
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Development of CD4+CD8+ thymocytes in RAG-deficient mice through a T cell receptor beta chain-independent pathway.RAG缺陷小鼠中CD4+CD8+胸腺细胞通过不依赖T细胞受体β链的途径发育。
J Exp Med. 1995 Mar 1;181(3):1187-95. doi: 10.1084/jem.181.3.1187.