PHOTOBIOLOGY OF VITAMIN D

维生素 D 的光生物学

• 批准号: 6345222
• 负责人: MICHAEL F HOLICK
• 金额: $ 0.49万
• 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/6345222
• 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 MS的免疫学方面的重点是定义 抗原与该抗原产生免疫反应，并 分子负责呈递这些抗原。 对于许多人 多年，教条一直是T细胞识别肽抗原 在M11C分子和大量研究的背景下提出 已经定义了可能有助于发病机理的肽抗原 MS。 最近，它表明CD1家族的分子 可以充当脂质抗原演示中的限制元素 T细胞的专门子集表明频谱 T细胞反应的抗原可能比以前更广泛 想法。 因此，有关这些抗原鉴定的研究 远只针对细菌成分。 CD1糖蛋白是 细胞表面分子，与beta2-微球蛋白无关 与主要组织相容性（M11C）抗原在结构上相关。 CD I系列包括CD I A，B和C蛋白，产品的产品 所有映射到染色体1的单独基因，具有分子质量 分别为49、45和43 kDa。 它们在所有皮质上都发现 胸腺细胞，但不在循环的T细胞或单核细胞上，并且是 通过树突状细胞亚群的差异表达， Langerhans细胞（CDI A和CD I C），B细胞的子集（CD I C）， 某些炎症中的某些T细胞白血病和组织巨噬细胞 病变。 在大脑中，有些人已经报道了CD a的小胶质细胞 调查人员，但没有其他人。 Battistini等人表明 CDLB在活性MS病变中表达。 尤其是脂质 糖脂，是髓鞘膜的主要组成部分 合理地认为脂质可能参与 MS的免疫病理学。 免疫反应包括CD1 将脂质抗原呈现到专门种群的分子 T细胞。 为了检验这一假设，第一步是隔离和 表征引起T细胞反应的纯化脂质抗原。 最近的工作表明，引起最大的糖脂 反应包含异常的脂肪酸和长链碱基。 所以， 重要的是要找到异常的脂肪酸或长链碱是否是 在MS组织中表达。