Molecular Aspects of Human CD1d Functions

人类 CD1d 功能的分子方面

• 批准号: 7012765
• 负责人: PETER CRESSWELL
• 金额: $ 27.94万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-02-01 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7012765
• 关键词: CD1 molecule; CHO cells; MHC class II antigen; SDS polyacrylamide gel electrophoresis; T lymphocyte; affinity chromatography; antibody specificity; electrospray ionization mass spectrometry; endocytosis; endoplasmic reticulum; flow cytometry; glycoprotein biosynthesis; glycoproteins; immunofluorescence technique; immunoprecipitation; lipid biosynthesis; liquid chromatography; mass spectrometry; membrane proteins; molecular shape; protein binding

DESCRIPTION (provided by applicant): CD 1 molecules are cell surface glycoproteins homologous to MHC class I molecules that present autologous or antigenic lipids to specific T cells. In humans there are five CD1 genes and one of them, encoding CD1d molecules, is also present in mice. CD1d molecules are specifically recognized by a subset of T lymphocytes called NKT cells that play an important role in resistance to infection by producing large quantities of gamma-interferon or interleukin-4 when stimulated. The processing mechanisms responsible for mediating lipid association with CD 1d molecules are unknown. This proposal seeks to understand the mechanisms governing the association of lipids with assembling human CD 1d glycoproteins in the endoplasmic reticulum as well as during their passage through the endocytic pathway. The spectrum of lipids bound in each of these compartments will be identified as well as co-factors mediating the acquisition of these lipids. A subset of CD 1d molecules binds to assembling MHC class II glycoproteins in the endoplasmic reticulum and this interaction is maintained on the cell surface. Three potential effects of this association will be examined: alteration of the repertoire of peptides bound to MHC class II molecules; alteration of the repertoire of lipids bound to CD 1d molecules; and enhanced recognition of cell surface CD 1d-lipid complexes by CD4-positive, CD 1d-reactive T cells. Possible effects of a variety of stimuli, including stress responses and viral infection, on the recognition of CD 1d-expressing cells by CD 1d-restricted T lymphocytes and on the repertoire of CD 1d-associated lipids will also be examined.

描述（由申请人提供）：CD 1分子是与MHC I类分子同源的细胞表面糖蛋白，它们呈现了特定T细胞的自体或抗原脂质。在人类中，有五个CD1基因，其中一个编码CD1D分子也存在于小鼠中。 CD1D分子由称为NKT细胞的T淋巴细胞的子集特异性识别，这些T淋巴细胞在抗感染中起着重要作用，在刺激时通过产生大量的伽马互动或interleukin-4在抗性感染中起重要作用。负责介导脂质与CD 1D分子的处理机制尚不清楚。该提案旨在理解脂质与组装人CD 1D糖蛋白在内质网中以及通过内吞途径的通过时的机制。将识别在每个隔室中结合的脂质的光谱以及介导这些脂质的获取的共同因素。 CD 1D分子的子集与内质网中组装MHC II类糖蛋白结合，并将这种相互作用保持在细胞表面上。将研究这种关联的三个潜在影响：与MHC II类分子结合的肽曲目的改变；与Cd 1d分子结合的脂质曲目的改变；并通过CD4阳性CD 1D反应性T细胞增强了对细胞表面CD 1D脂质复合物的识别。还将检查多种刺激，包括压力反应和病毒感染，对CD 1D限制的T淋巴细胞表达CD 1D细胞的可能影响以及对CD 1D相关脂质的曲目的识别。