HLA-DQA2 and HLA-DQB2 Genes Are Specifically Expressed in Human Langerhans Cells and Encode a New HLA Class II Molecule
HLA-DQA2 and HLA-DQB2 Genes Are Specifically Expressed in Human Langerhans Cells and Encode a New HLA Class II Molecule
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DOI：
10.4049/jimmunol.1103048
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发表时间：
2012-04-15
影响因子：
4.4
通讯作者：
Tourne, Sylvie
中科院分区：
文献类型：
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作者：
Lenormand, Cedric;Bausinger, Huguette;Tourne, Sylvie
人类表皮朗格汉斯细胞（LCs）在免疫应答中的确切作用备受争议。在研究这些细胞的基因表达谱时，我们很感兴趣地发现HLA-DQB2基因可能在lc中表达。尽管它们的序列具有很强的进化保守性，但与HLA-DQA1/HLA-DQB1基因相似的低多态性HLA-DQA2/HLA-DQB2基因的伴随表达从未在任何细胞类型中被检测到。我们通过RT-PCR证实，HLA-DQA2和-DQB2基因都在lc中表达，但在单核细胞来源的树突状细胞、血液CD1c（+）或浆细胞样树突状细胞中不表达。HLA-DQ β 2链在lc中的存在可以通过Western blotting证实，而免疫荧光显示其定位于早期核内体。与其他HLA II类分子一样，HLA-DQ α 2和-DQ β 2链形成异源二聚体，必须与不变链结合才能到达内体区室。HLA-DQ α 2/ β 2异源二聚体在细胞表面表达，介导葡萄球菌超抗原刺激T细胞。有趣的是，HLA-DQ α 2和HLA-DQ β 1链形成混合异源二聚体，有效地离开内质网。这些观察结果强烈表明，低多态性的HLA-DQA2和-DQB2基因应被认为具有免疫学重要性。HLA-DQ α 2/ β 2分子可以影响lc呈现的Ags库的复杂性。中华免疫学杂志，2012,18(8):3903- 39011。
The precise role of human epidermal Langerhans cells (LCs) in immune response is highly controversial. While studying the gene expression profile of these cells, we were intrigued to identify the HLA-DQB2 gene as potentially expressed in LCs. Despite a strong evolutionary conservation of their sequences, the concomitant expression of the poorly polymorphic HLA-DQA2/HLA-DQB2 genes, paralogous to the HLA-DQA1/HLA-DQB1 genes, has never been detected in any cell type. We confirmed by RT-PCR that the HLA-DQA2 and -DQB2 genes are both expressed in LCs, but not in monocyte-derived dendritic cells, or in blood CD1c(+) or plasmacytoid dendritic cells. The presence of the HLA-DQ beta 2 chain in LCs could be demonstrated by Western blotting, whereas immunofluorescence revealed its localization in early endosomes. As in the case of other HLA class II molecules, the HLA-DQ alpha 2 and -DQ beta 2 chains formed heterodimers that had to associate with the invariant chain to reach endosomal compartments. HLA-DQ alpha 2/beta 2 heterodimers were expressed at the cell surface, where they could mediate staphylococcal superantigen stimulation of T cells. Interestingly, HLA-DQ alpha 2 and HLA-DQ beta 1 chains formed mixed heterodimers which efficiently left the endoplasmic reticulum. These observations strongly suggest that the poorly polymorphic HLA-DQA2 and -DQB2 genes should be considered to be of immunological importance. The HLA-DQ alpha 2/beta 2 molecules could influence the complexity of the repertoire of Ags presented by LCs. The Journal of Immunology, 2012, 188: 3903-3911.