CD1-lipid reactivity of epidermal T cells

描述（由申请人提供）：自最初发现？30年前，非经典MHC分子被提出作为这些细胞的抗原或抗原提呈分子。在这期间的几年里，个体T细胞克隆已被鉴定出对CD1和TL分子具有反应性，但MHC反应性尚未显示在？�细胞。最近来自两个小组的数据显示，V？1+ TCR来自人外周血和肠道？细胞可以直接结合CD1d-？GalCer和cd1 -硫脂。有趣的是，V？1+ TCR也用于表皮驻留？人类和老鼠皮肤中的细胞。在皮肤炎症和疾病期间，CD1在表皮细胞上的表达上调，而表皮是脂质和皮肤油脂的丰富来源。这提出了一种可能性，即cd1 -脂质反应性可能是所有V？1+ T细胞，包括居住在表皮的细胞。我们提议验证这样一种假设，即cd1皮肤脂质抗原可以向邻近的表皮细胞提供损伤或疾病的应激信号。激活1+ T细胞的伤口愈合功能。我们将通过确定人类或小鼠V？1+ TCR可以与cd1脂质抗原相互作用，并通过研究伤口愈合过程中CD1d的表达是否影响表皮？-细胞伤口愈合反应。如果被发现是一个典型的压力信号？细胞活化、CD1或皮肤脂质可能被认为是未来改善慢性伤口愈合以及其他皮肤炎症或自身免疫性疾病策略的目标。

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.