Skint-1 is a highly specific, unique selecting component for epidermal T cells
Skint-1 is a highly specific, unique selecting component for epidermal T cells
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DOI：
10.1073/pnas.1010890108
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发表时间：
2011-02-22
影响因子：
11.1
通讯作者：
Hayday, Adrian C.
中科院分区：
文献类型：
--
作者：
Barbee, Susannah D.;Woodward, Martin J.;Hayday, Adrian C.
α β T细胞库选择由胸腺上皮细胞或骨髓细胞呈递的肽-MHC复合物和胸腺细胞表达的脂质-CD 1复合物介导。相比之下，γ δ T细胞库选择在很大程度上尚未解决。Skint-1是一种独特的IG超家族基因，突变的小鼠不发育典型的V γ 5V δ 1（+）树突状表皮T细胞。这项研究表明，转基因Skint-1，在广泛的表达水平，精确和选择性地确定V γ 5V δ 1（+）树突状表皮T细胞区室。Skint-1由胸腺髓质上皮细胞表达，与脂质-CD 1复合物不同，必须由基质细胞表达才能有效发挥功能。其不寻常的跨膜-胞质区域严重限制了细胞表面表达，但增加这种表达，或者相反，保留Skint-1细胞内显着损害功能。每个Skint 1域似乎是非冗余的，包括一个独特的十聚体指定IgV域处理。Skint-1生物学的这项调查指出了支持上皮内γ δ基因库的阳性选择的复杂事件。
alpha beta T-cell repertoire selection is mediated by peptide-MHC complexes presented by thymic epithelial or myeloid cells, and by lipid-CD1 complexes expressed by thymocytes. gamma delta T-cell repertoire selection, by contrast, is largely unresolved. Mice mutant for Skint-1, a unique Ig superfamily gene, do not develop canonical V gamma 5V delta 1(+) dendritic epidermal T cells. This study shows that transgenic Skint-1, across a broad range of expression levels, precisely and selectively determines the V gamma 5V delta 1(+) dendritic epidermal T-cell compartment. Skint-1 is expressed by medullary thymic epithelial cells, and unlike lipid-CD1 complexes, must be expressed by stromal cells to function efficiently. Its unusual transmembrane-cytoplasmic regions severely limit cell surface expression, yet increasing this or, conversely, retaining Skint-1 intracellularly markedly compromises function. Each Skint1 domain appears nonredundant, including a unique decamer specifying IgV-domain processing. This investigation of Skint-1 biology points to complex events underpinning the positive selection of an intraepithelial gamma delta repertoire.