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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。

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