CD1-lipid reactivity of epidermal T cells

描述（由申请人提供）：自首次发现？� 30年前，非经典MHC分子被提议作为这些细胞的抗原或抗原呈递分子。在此期间的几年里，个别T细胞克隆已被确定与CD 1和TL分子的反应，但MHC反应性尚未显示？� 细胞最近的数据从两组现在已经表明，V？1+ TCR来自人外周血和肠道？� 细胞可以直接与CD 1d-？GalCer和CD 1d-硫苷脂。有趣的是，V？1+ TCR也被表皮居民使用？� 人类和小鼠皮肤中的细胞。在皮肤炎症和疾病期间，表皮细胞上的CD 1表达上调，并且表皮是脂质和皮肤油的丰富来源。这提出了可能性，即CD 1-脂质反应可能是所有V？1+ T细胞，包括驻留在表皮中的那些。我们建议测试的假设，CD 1-皮肤脂质抗原可以提供一个应力信号的损伤或疾病的表皮相邻的V？1+ T细胞激活其伤口愈合功能。我们将测试这一假设，确定是否人或小鼠V？1+ TCR可以与CD 1-脂质抗原相互作用，并通过研究伤口愈合过程中CD 1d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、CD 1或皮肤脂质可以被认为是未来策略的目标，以改善慢性伤口以及其他皮肤炎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.