Molecular Aspects of Human CD1d Functions

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，其将自体或抗原性脂质呈递给特异性T细胞。在人类中有五个CD 1基因，其中一个编码CD 1d分子，也存在于小鼠中。CD 1d分子被称为NKT细胞的T淋巴细胞亚群特异性识别，NKT细胞在刺激时通过产生大量γ-干扰素或白细胞介素-4在抵抗感染中发挥重要作用。负责介导脂质与CD 1d分子结合的加工机制尚不清楚。该提案旨在了解脂质与内质网中组装的人CD 1d糖蛋白以及它们通过内吞途径期间的关联的管理机制。将鉴定这些隔室中的每一个中结合的脂质的谱以及介导这些脂质的获得的辅因子。CD 1d分子的一个亚组与内质网中组装的MHC II类糖蛋白结合，这种相互作用维持在细胞表面。将检查这种关联的三个潜在影响：改变与MHC II类分子结合的肽库;改变与CD 1d分子结合的脂质库;以及增强CD 4阳性、CD 1d反应性T细胞对细胞表面CD 1d-脂质复合物的识别。各种刺激，包括应激反应和病毒感染，对CD 1d-限制性T淋巴细胞的CD 1d-表达细胞的识别和CD 1d-相关脂质的库的可能影响也将进行检查。

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.