Langerhans Cells Transfer Targeted Antigen to Dermal Dendritic Cells and Acquire Major Histocompatibility Complex II In Vivo.
Langerhans Cells Transfer Targeted Antigen to Dermal Dendritic Cells and Acquire Major Histocompatibility Complex II In Vivo.
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朗格汉斯细胞将靶向抗原转移至真皮树突细胞并在体内获得主要组织相容性复合物 II。
DOI：
10.1016/j.jid.2018.02.005
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Kaplan,DanielH
中科院分区：
文献类型：
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作者：
Yao,Chen;Kaplan,DanielH
皮肤中的树突状细胞（dc）对病原体的适应性免疫反应的发展和外周耐受性的维持至关重要（Kashem等人，2017）。在稳态条件下，至少有四种皮肤dc亚群具有特征：表皮朗格汉斯细胞（LC）、真皮经典DC1 （cDC1，也称为CD103+ dDC）、真皮cDC2（也称为CD11b+ dDC）和CD103 - CD11b双阴性dc。虽然每个DC子集的功能专门化已经得到了很好的研究，但这些DC子集在稳态条件下的功能相互作用却知之甚少。使用c型凝集素受体特异性单克隆抗体靶向DC抗原，是研究DC靶群体体内抗原呈递适应性反应的有效方法，目前正在开发用于治疗性疫苗接种（Steinman和Banchereau， 2007）。我们之前开发了BAC转基因小鼠（huLang），在表皮LC上选择性表达人Langerin，一种c型凝集素受体（Bobr等，2010）。用低至0.05 μg的α-huLangerin mAb偶联2W1S模型抗原（α-huLang-2W1S）免疫这些小鼠，有效且选择性地靶向LCs，导致内源性2W1S特异性CD4+ T细胞扩增，可使用2W1S: IA b四聚体检测（Yao et al., 2015）。
Dendritic cells (DCs) in the skin are critical for the development of adaptive immune responses to pathogens and for the maintenance of peripheral tolerance (Kashem et al., 2017). Under steady-state conditions, at least four subsets of cutaneous DCs have been characterized: epidermal Langerhans cells (LC), dermal classical DC1 (cDC1, also known as CD103+ dDC), dermal cDC2 (also known as CD11b+ dDC), and CD103–CD11b–double-negative DCs. Although functional specializations of each DC subset have been well studied, the functional interaction between these DC subsets under steady-state conditions is poorly understood.Targeting antigen to DC using monoclonal antibodies specific for C-type lectin receptors offers an efficient method to study adaptive responses to antigen presentation by targeted populations of DCs in vivo, and is being developed for therapeutic vaccinations (Steinman and Banchereau, 2007). We have previously developed BAC transgenic mice (huLang) with selective expression of human Langerin, a C-type lectin receptor, on epidermal LC (Bobr et al., 2010). Immunization of these mice with as little as 0.05 μg of α-huLangerin mAb conjugated to the 2W1S model antigen (α-huLang-2W1S) efficiently and selectively targeted LCs, resulting in expansion of endogenous 2W1S-specific CD4+ T cells, which could be detected using 2W1S: IA b tetramer (Yao et al., 2015).