CD1-lipid reactivity of epidermal T cells

描述(申请人提供)：自从30年前首次发现�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，但尚未显示出对�细胞群体的MHC反应性。最近来自两组的数据表明，来自人外周血和肠道�细胞的V？1+TcR可以直接与CD1d-半乳糖和CD1d-硫脂结合。有趣的是，V？1+TcR也被人类和小鼠皮肤中的表皮驻留�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CD1-脂质反应性可能是所有V？1+T细胞的特征，包括那些驻留在表皮的T细胞。我们提出的假设是，CD1皮肤脂肪抗原可以向邻近的V？1+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的V？1+TcR是否能与CD1-脂类抗原相互作用，以及通过研究伤口愈合过程中CD1d的表达是否影响表皮�细胞的伤口愈合反应来检验这一假设。如果被发现是�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靶点，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 ?� 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 ?� cells. Recent data from two groups has now shown that the V?1+ TCR from human peripheral blood and intestinal ?� cells can directly bind to CD1d-?GalCer and CD1d-sulfatide. Interestingly, the V?1+ TCR is also used by epidermal-resident ?� 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 V?1+ 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 V?1+ T cells to activate their wound healing functions. We will test this hypothesis by determining if the human or mouse V?1+ TCR can interact with CD1-lipid antigens and by investigating whether CD1d expression during wound healing impacts epidermal ?� cell wound healing responses. If found to be a prototypic stress-signal for ?� 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.