PHOTOBIOLOGY OF VITAMIN D

维生素 D 的光生物学

• 批准号: 6478946
• 负责人: MICHAEL F HOLICK
• 金额: $ 5.36万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6478946
• 关键词: biological products; biomaterials; biomedical resource; genetics; immunology; inflammation; lipids; nervous system; structural biology; technology /technique

Multiple sclerosis (MS) is a T-cell mediated autoimmune disease of the central nervous system (CNS). Much research related to the immunological aspects of MS has focused on defining the nature of the antigen(s) against which the immune response is generated and the molecule(s) responsible for presentation of these antigens. For many years, the dogma has been that T-cells recognize peptide antigens presented in the context of M11C molecules and substantial research has defined peptide antigens that may contribute to the pathogenesis of MS. Recently, it hasbeen shown that molecules of the CD1 family can act as restriction elements in lipid antigen presentations to specialized subsets of T-cells suggesting that the spectrum of antigens to which T-cells respond may be broader than previously thought. Studies on the identification of these antigens have thus far been directed only to bacterial components. CD1 glycoproteins are cell surface molecules, noncovalently linked to beta2-microglobulin and structurally related to major histocompatibility (M11C) antigens. The CD I family includes CD I a, b and c proteins, products of separate genes that all map to chromosome 1, having molecular masses of 49, 45, and 43 kDa respectively. They are found on all cortical thymocytes, but not on circulating T-cells or monocytes, and are differentially expressed by subpopulations of dendritic cells, Langerhans cells (CDI a and CD I c), subsets of B-cells (CD I c), certain T-cell leukemias, and tissue macrophages in some inflammatory lesions. In the brain, CD I a has been reported on microglia by some investigators, but not others. Battistini et al.. have shown that CDlb, is expressed in active MS lesions. Since lipids, particularly glycolipids, are a major component of the myelin membrane it is reasonable to consider that lipids may be involved in the immunopathology of MS. The immune response would include CD1 molecules presenting lipid antigens to specialized populations of T-cells. To test this hypothesis, the first step is to isolate and characterize a purified lipid antigen that elicits a T-cell response. Recent work has suggested that the glycolipids that elicit the most response contain unusual fatty acids and long chain bases. Therefore, it is important to find if unusual fatty acids or long chain bases are expressed in MS tissues.

多发性硬化症（MS）是一种T细胞介导的自身免疫性疾病， 中枢神经系统（CNS）。 许多研究与 多发性硬化症的免疫学方面侧重于定义多发性硬化症的性质。 针对其产生免疫应答的抗原， 负责呈递这些抗原的分子。 对于许多 多年来，一直认为T细胞识别肽抗原 在M11 C分子和大量研究的背景下提出的 已经确定了可能导致发病的肽抗原 最近，研究表明，CD 1家族的分子 可以作为脂质抗原呈递中的限制性元件， 特化的T细胞亚群表明， T细胞应答的抗原可能比以前更广泛 想的 因此，对这些抗原的鉴定的研究 迄今为止仅涉及细菌成分。 CD 1糖蛋白是 细胞表面分子，与β 2-微球蛋白非共价连接 并且在结构上与主要组织相容性（M11 C）抗原相关。 CD I家族包括CD I a、B和c蛋白， 分离的基因都映射到1号染色体，具有分子质量 分别为49、45和43 kDa。 它们存在于大脑皮层 胸腺细胞，但不是循环T细胞或单核细胞， 树突细胞亚群的差异表达， 朗格汉斯细胞（CDIa和CDIc），B细胞亚群（CDIc）， 某些T细胞白血病和组织巨噬细胞在一些炎症 病变 在大脑中，CD I a已经被一些人报道在小胶质细胞上 调查员，而不是其他人。 Battistini et al. 表明 CDlb在活动性MS病变中表达。 由于脂质，特别是 糖脂是髓鞘膜的主要成分， 合理地认为脂质可能参与了 免疫反应包括CD 1 将脂质抗原呈递给特定的 T细胞 为了验证这一假设，第一步是分离和 表征激发T细胞应答的纯化的脂质抗原。 最近的研究表明，糖脂，引起最 反应含有不寻常的脂肪酸和长链碱。 因此，我们认为， 重要的是要发现，如果不寻常的脂肪酸或长链碱， 在MS组织中表达。