Location of major histocompatibility complex class II molecules in rafts on dendritic cells enhances the efficiency of T-cell activation and proliferation
Location of major histocompatibility complex class II molecules in rafts on dendritic cells enhances the efficiency of T-cell activation and proliferation
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DOI：
10.1111/j.1365-3083.2006.01700.x
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发表时间：
2006-01-01
影响因子：
3.7
通讯作者：
Lombardi, G
中科院分区：
文献类型：
--
作者：
Eren, E;Yates, J;Lombardi, G
树突状细胞(DC)中存在主要组织相容性复合体(MHC)II类分子，但其在T细胞活化中的重要性尚不清楚。本研究对人单核细胞来源的DC中的脂筏成分(CD59和GM1神经节苷脂)的分布进行了研究。DC的这些成分在细胞表面分布均匀。此外，RAFT相关的GM1神经节苷脂与交联型MHCⅡ类分子共定位。这意味着RAFT组分与这些MHC分子共聚集，这可能在T细胞与抗原提呈细胞之间的相互作用中起重要作用。在研究DC：T细胞相互作用对RAFT分布的影响的研究中，我们发现脂质RAFT成分CD59聚集在突触界面的DC上，并伴随着相互作用的T细胞的激活。在DC和CD4(+)T细胞克隆之间的抗原特异性反应中，脂筏的破坏导致CD59聚集和T细胞激活的抑制。当使用限量的同源多肽时，这一点最为明显。综上所述，这些数据表明在DC：T细胞相互作用过程中，MHC II类分子与脂筏有关，并提示DC脂筏在T细胞活化中起重要作用。
The existence of major histocompatibility complex (MHC) class II molecules in lipid rafts has been described in dendritic cells (DC); however, the importance of rafts in T-cell activation has not been clarified. In this study, the distribution of the lipid raft components (CD59 and GM1 ganglioside) in human monocyte-derived DC was investigated. DC had an even distribution of these components at the cell surface. In addition, raft-associated GM1 ganglioside colocalized with cross-linked MHC class II. This implies coaggregation of raft components with these MHC molecules, which may be important in the interaction between T cells and antigen-presenting cells. In studies carried out to investigate the effect of the DC : T-cell interaction on raft distribution, we found a clustering of the lipid raft component CD59 on DC at the synaptic interface, with associated activation of the interacting T cell. In an antigen-specific response between DC and CD4(+) T-cell clones, disruption of lipid rafts resulted in inhibition of both CD59 clustering and T-cell activation. This was most pronounced when limiting amounts of cognate peptide were used. Together, these data demonstrate the association of MHC class II with lipid rafts during DC : T-cell interaction and suggest an important role for DC lipid rafts in T-cell activation.