Distinct subsets of CD1d-restricted T cells recognize self-antigens loaded in different cellular compartments.
Distinct subsets of CD1d-restricted T cells recognize self-antigens loaded in different cellular compartments.
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DOI：
10.1084/jem.189.1.103
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发表时间：
1999-01-04
期刊：
影响因子：
--
通讯作者：
Bendelac A
中科院分区：
文献类型：
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作者：
Chiu YH;Jayawardena J;Weiss A;Lee D;Park SH;Dautry-Varsat A;Bendelac A
尽管最近的研究表明，主要的组织相容性复合物样、β2-微球蛋白相关的 CD1 分子可能具有向 α/β T 细胞呈递一种新型化学抗原、脂质和糖脂的功能，但人们对与 CD1 相互作用的 T 细胞亚群知之甚少。最近鉴定出了表达 CD1d 自身反应性、自然杀伤 (NK)1.1 受体的 α/β T 细胞的子集。这些细胞包括 CD4−CD8− 和 CD4+ T 细胞，在小鼠中优先使用不变的 Vα14-Jα281 T 细胞受体 (TCR) α 链与 Vβ8 TCR β 链配对，或在人类中使用同源的 Vα24-JαQ/Vβ11。该细胞亚群在 TCR 参与后可爆发性释放关键细胞因子，例如白细胞介素 (IL)-4 和干扰素 (IFN)-γ，并可调节多种感染和自身免疫性疾病。在这里，我们报告了第二个 CD1d 限制性 CD4+ T 细胞亚群的存在，它们不表达 NK1.1 受体或 Vα14 TCR。与 Vα14+ NK1.1+ T 细胞一样，这些 T 细胞对 CD1d 表现出高频率的自身反应，使用一组有限但不同的 TCR 基因家族，并有助于静脉注射抗 CD3 诱导的 IL-4 和 IFN-γ 的早期爆发。然而，Vα14+ NK1.1+ 和 Vα14− NK1.1− T 细胞对自身抗原呈递的要求显着不同。抗原呈递至 Vα14+ NK1.1+ 细胞需要通过尾部编码的基于酪氨酸的基序内体靶向 CD1d，而抗原呈递至 Vα14− NK1.1− 细胞则不需要。这些实验表明存在两个表型不同的 CD1d 限制性 T 细胞子集，它们调查加载在不同细胞区室中的自身抗原。
Although recent studies have indicated that the major histocompatibility complex–like, β2-microglobulin–associated CD1 molecules might function to present a novel chemical class of antigens, lipids and glycolipids, to α/β T cells, little is known about the T cell subsets that interact with CD1. A subset of CD1d-autoreactive, natural killer (NK)1.1 receptor–expressing α/β T cells has recently been identified. These cells, which include both CD4−CD8− and CD4+ T cells, preferentially use an invariant Vα14-Jα281 T cell receptor (TCR) α chain paired with a Vβ8 TCR β chain in mice, or the homologous Vα24-JαQ/Vβ11 in humans. This cell subset can explosively release key cytokines such as interleukin (IL)-4 and interferon (IFN)-γ upon TCR engagement and may regulate a variety of infectious and autoimmune conditions. Here, we report the existence of a second subset of CD1d-restricted CD4+ T cells that do not express the NK1.1 receptor or the Vα14 TCR. Like the Vα14+ NK1.1+ T cells, these T cells exhibit a high frequency of autoreactivity to CD1d, use a restricted albeit distinct set of TCR gene families, and contribute to the early burst of IL-4 and IFN-γ induced by intravenous injection of anti-CD3. However, the Vα14+ NK1.1+ and Vα14− NK1.1− T cells differ markedly in their requirements for self-antigen presentation. Antigen presentation to the Vα14+ NK1.1+ cells requires endosomal targeting of CD1d through a tail-encoded tyrosine-based motif, whereas antigen presentation to the Vα14− NK1.1− cells does not. These experiments suggest the existence of two phenotypically different subsets of CD1d-restricted T cells that survey self-antigens loaded in distinct cellular compartments.