MHC class II-peptide complexes in dendritic cell lipid microdomains initiate the CD4 Th1 phenotype
MHC class II-peptide complexes in dendritic cell lipid microdomains initiate the CD4 Th1 phenotype
复制标题
DOI：
10.4049/jimmunol.171.11.5812
复制
发表时间：
2003-12-01
影响因子：
4.4
通讯作者：
Machy, P
中科院分区：
文献类型：
--
作者：
Buatois, V;Baillet, M;Machy, P
我们研究了CD 4 T细胞对骨髓来源的树突状细胞（DC）与MHC II类（MHC II）分子联合呈递的抗原的反应分化。被IgG调理的脂质体中包封的肽通过内吞作用被摄取。响应于该Ag的MHC II肽特异性T细胞以CD 40-、CD 28-、MyD 88-和IL-12依赖性方式极化至Th 1细胞因子谱。从暴露于相同DC的相同转基因T细胞群体获得Th 2应答，在所述DC上，MHC-肽复合物在摄取FcR靶向脂质体后分散48小时。DC吸收相同的FcR靶向脂质体，然后暴露于甲基-β-环糊精，其螯合胆固醇并解离脂质微区，也刺激Th 2分化。与直接结合到MHC 11的肽孵育的DC一起孵育T细胞导致Th 2应答，无论DC是否与作为成熟刺激物的调理脂质体共孵育。因此，CD 4 Th 1极化似乎取决于DC脂质微区中的MHC II-肽复合物簇集以及肽加载和T细胞相遇之间的时间。
We investigated differentiation of CD4 T cells responding to Ag presented by bone marrow-derived dendritic cells (DC) in association with MHC class II (MHC II) molecules. Peptides encapsulated in liposomes opsonized by IgG were taken up by endocytosis. MHC II-peptide-specific T cells responding to this Ag were polarized to a Th1 cytokine profile in a CD40-, CD28-, MyD88-, and IL-12-dependent manner. Th2 responses were obtained from the same transgenic T cell population exposed to the same DC on which MHC-peptide complexes had dispersed for 48 h following uptake of FcR-targeted liposomes. DC that took up the same FcR-targeted liposomes and then were exposed to methyl-beta-cyclodextrin, which chelates cholesterol and dissociates lipid microdomains, also stimulated Th2 differentiation. Incubation of T cells with DC incubated with peptides directly binding to MHC 11 resulted in Th2 responses, whether or not the DC were coincubated with opsonized liposomes as a maturation stimulus. CD4 Th1 polarization thus appears to depend on MHC II-peptide complex clustering in DC lipid microdomains and the time between peptide loading and T cell encounter.