After two decades of the study of lipid antigens that activate CD1-restricted T cells, new studies show how autoreactive αβ T-cell receptors (TCRs) can directly recognize the outer surface of CD1 proteins in ways that are lipid-agnostic. Most recently, this lipid agnosticism has turned to negativity, with the discovery of natural CD1 ligands that dominantly negatively block autoreactive αβ TCR binding to CD1a and CD1d. This review highlights the basic differences between positive and negative regulation of cellular systems. We outline strategies to discover lipid inhibitors of CD1-reactive T cells, whose roles in vivo are becoming clear, especially in CD1-mediated skin disease.

经过二十年对激活 CD1 限制性 T 细胞的脂质抗原的研究，新的研究表明自身反应性 αβ T 细胞受体 (TCR) 如何以脂质不可知的方式直接识别 CD1 蛋白的外表面。最近，随着天然 CD1 配体的发现，这种脂质不可知论已转向消极性，该配体主要消极地阻断自身反应性 αβ TCR 与 CD1a 和 CD1d 的结合。这篇综述强调了细胞系统的正向调节和负向调节之间的基本区别。我们概述了发现 CD1 反应性 T 细胞脂质抑制剂的策略，其在体内的作用正变得越来越清楚，特别是在 CD1 介导的皮肤病中。