Composition of MHC class II‐enriched lipid microdomains is modified during maturation of primary dendritic cells
Composition of MHC class II‐enriched lipid microdomains is modified during maturation of primary dendritic cells
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原代树突状细胞成熟过程中富含 MHC II 类脂质微结构域的组成发生改变
DOI：
10.1189/jlb.0103045
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发表时间：
2003
影响因子：
5.5
通讯作者：
N. Mooney
中科院分区：
文献类型：
--
作者：
N. Setterblad;C. Roucard;C. Bocaccio;J. Abastado;D. Charron;N. Mooney
树突状细胞（Dendritic cells，DC）是目前发现的最有效的抗原提呈细胞。主要组织相容性复合体（MHC）II类分子表达随成熟而变化;未成熟DC在细胞内浓缩MHC II类分子，而成熟增加MHC II类和共刺激分子的表面表达以优化抗原呈递。在B淋巴细胞和THP-1单核细胞系中，已经描述了通过位于脂质微区的MHC II类分子的信号转导。我们已经在整个人DC成熟过程中表征了MHC II类分子，特别注意它们在富含脂质的微结构域中的定位。只有未成熟的DC表达空的MHC II类分子，并且成熟增加了肽结合的异源二聚体的水平。配体与表面人类白细胞抗原（HLA）-DR的结合诱导未成熟DC的快速内化。未成熟DC中细胞表面洗涤剂不溶性鞘糖脂富集的微区簇HLA-DR的比例较高，尽管成熟DC中HLA-DR的表面表达较高。在未成熟DC中，含有HLA-DR的微结构域的成分包括src激酶林恩和细胞骨架蛋白微管蛋白。成熟改变了含HLA-DR-微区的组成，包括蛋白激酶C（PKC）-δ、林恩和细胞骨架蛋白肌动蛋白，伴随着微管蛋白的丢失。通过HLA-DR的信号转导重新分布了HLA-DR和-DM以及PKC-δ，并丰富了成熟DC微区的肌动蛋白含量。因此，由于DC成熟导致的HLA-DR表达增加伴随着HLA-DR空间组织的改变。这种调节可能有助于在未成熟与成熟DC中由与MHC II类分子结合的配体诱导的不同应答。
Dendritic cells (DCs) are the most potent antigen presenting cells. Major histocompatibility complex (MHC) class II molecule expression changes with maturation; immature DCs concentrate MHC class II molecules intracellularly, whereas maturation increases surface expression of MHC class II and costimulatory molecules to optimize antigen presentation. Signal transduction via MHC class II molecules localized in lipid microdomains has been described in B lymphocytes and in the THP‐1 monocyte cell line. We have characterized MHC class II molecules throughout human DC maturation with particular attention to their localization in lipid‐rich microdomains. Only immature DCs expressed empty MHC class II molecules, and maturation increased the level of peptide‐bound heterodimers. Ligand binding to surface human leukocyte antigen (HLA)‐DR induced rapid internalization in immature DCs. The proportion of cell‐surface detergent‐insoluble glycosphingolipid‐enriched microdomain‐clustered HLA‐DR was higher in immature DCs despite the higher surface expression of HLA‐DR in mature DCs. Constituents of HLA‐DR containing microdomains included the src kinase Lyn and the cytoskeletal protein tubulin in immature DCs. Maturation modified the composition of the HLA‐DR‐containing microdomains to include protein kinase C (PKC)‐δ, Lyn, and the cytoskeletal protein actin, accompanied by the loss of tubulin. Signaling via HLA‐DR redistributed HLA‐DR and ‐DM and PKC‐δ as well as enriching the actin content of mature DC microdomains. The increased expression of HLA‐DR as a result of DC maturation was therefore accompanied by modification of the spatial organization of HLA‐DR. Such regulation could contribute to the distinct responses induced by ligand binding to MHC class II molecules in immature versus mature DCs.
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DOI：
10.1073/pnas.96.26.15050
发表时间：
1999-12-21
影响因子：
11.1
作者：
Santambrogio, L;Sato, AK;Stern, LJ
通讯作者：
Stern, LJ
影响因子：
32.4
作者：
Villalba, M;Coudronniere, N;Altman, A
通讯作者：
Altman, A
影响因子：
32.4
作者：
R. Xavier;Todd Brennan;Qingqin Li;Christine McCormack;B. Seed
通讯作者：
R. Xavier;Todd Brennan;Qingqin Li;Christine McCormack;B. Seed
DOI：
10.1073/pnas.96.26.15056
发表时间：
1999-12-21
影响因子：
11.1
作者：
Santambrogio, L;Sato, AK;Stern, LJ
通讯作者：
Stern, LJ