CD1-lipid reactivity of epidermal T cells

描述(申请人提供)：自从30年前首次发现γδ细胞以来，非经典的MHC分子一直被认为是这些细胞的抗原或抗原提呈分子。在其间的几年中，单个T细胞克隆已被鉴定为对CD1和TL分子具有反应性，但在γδ细胞群体中尚未显示出MHC反应性。最近来自两组的数据表明，来自人外周血和肠道δ细胞的Vγδ1+TcR可以直接与CD1d-αGalCer和CD1d-硫脂结合。有趣的是，Vδ1+TcR也被人类和小鼠皮肤中的表皮驻留的γδ细胞所使用。在皮肤炎症和疾病期间，CD1在表皮细胞上的表达上调，表皮是脂类和皮肤油的丰富来源。这增加了一种可能性，即CD1-脂质反应性可能是所有Vδ1+T细胞的特征，包括那些驻留在表皮的细胞。我们建议检验这一假设，即CD1皮肤脂肪抗原可以向邻近的Vδ1+T细胞提供表皮损伤或疾病的应激信号，以激活它们的伤口愈合功能。我们将通过确定人或小鼠Vδ1+TcR是否能与CD1脂类抗原相互作用以及研究伤口愈合过程中CD1d的表达是否影响表皮γδ细胞伤口愈合反应来检验这一假说。如果被发现是γδ细胞激活的典型应激信号，CD1或皮脂可能被视为未来策略的目标，以促进慢性伤口以及其他皮肤炎症性或自身免疫性疾病的愈合。

DESCRIPTION (provided by applicant): Since the initial discovery of γδ cells 30 years ago, non-classical MHC molecules have been proposed as antigens or antigen presenting molecules for these cells. In the intervening years, individual T cell clones have been identified with reactivity to CD1 and TL molecules but MHC reactivity has not been shown for populations of γδ cells. Recent data from two groups has now shown that the Vδ1+ TCR from human peripheral blood and intestinal γδ cells can directly bind to CD1d-αGalCer and CD1d-sulfatide. Interestingly, the Vδ1+ TCR is also used by epidermal-resident γδ cells in both human and mouse skin. CD1 expression is upregulated on epidermal cells during skin inflammation and disease and the epidermis is a rich source of lipids and skin oils. This raises the possibility tha CD1-lipid reactivity may be characteristic of all Vδ1+ T cells, including those that are resident i the epidermis. We propose to test the hypothesis that CD1-skin lipid antigens can provide a stress-signal of damage or disease in the epidermis to neighboring Vδ1+ T cells to activate their wound healing functions. We will test this hypothesis by determining if the human or mouse Vδ1+ TCR can interact with CD1-lipid antigens and by investigating whether CD1d expression during wound healing impacts epidermal γδ cell wound healing responses. If found to be a prototypic stress-signal for γδ cell activation, CD1 or skin lipids may then be considered as targets in future strategies to improve healing of chronic wounds as well as other skin inflammatory or autoimmune diseases.