Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Centre for Plant Genomics and Biotechnology (UPM-INIA), Pozuelo de Alarcon, Madrid, Spain.
Clin Exp Allergy. 2017 Nov;47(11):1398-1408. doi: 10.1111/cea.12962. Epub 2017 Jul 14.
Recently, the nature of the lipid-ligand of Pru p 3, one of the most common plant food allergens in southern Europe, has been identified as a derivative of the alkaloid camptothecin bound to phytosphingosine. However, the origin of its immunological activity is still unknown.
We sought to evaluate the role of the Pru p 3 lipid-ligand in the immunogenic activity of Pru p 3.
In vitro cultures of different cell types (monocyte-derived dendritic cells [moDCs], PBMCs [peripheral blood mononuclear cells] and epithelial and iNKT-hybridoma cell lines) have been used to determine the immunological capacity of the ligand, by measuring cell proliferation, maturation markers and cytokine production. To study the capacity of the lipid-ligand to promote sensitization to Pru p 3 in vivo, a mouse model of anaphylaxis to peach has been produced and changes in the humoral and basophil responses have been analysed.
The lipid-ligand of Pru p 3 induced maturation of moDCsc and proliferation of PBMCs. Its immunological activity resided in the phytosphingosine tail of the ligand. The adjuvant activity of the ligand was also confirmed in vivo, where the complex of Pru p 3-ligand induced higher levels of IgE than Pru p 3 alone. The immunological capacity of the Pru p 3 ligand was mediated by CD1d, as maturation of moDCs was inhibited by anti-CD1d antibodies and Pru p 3-ligand co-localized with CD1d on epithelial cells. Finally, Pru p 3-ligand presented by CD1d was able to interact with iNKTs.
The Pru p 3 lipid-ligand could act as an adjuvant to promote sensitization to Pru p 3, through its recognition by CD1d receptors. This intrinsic adjuvant activity of the accompanying lipid cargo could be a general essential feature of the mechanism underlying the phenomenon of allergenicity.
最近，在欧洲南部最常见的植物性食物过敏原之一——普魯斯桃蛋白 3（Pru p 3）的脂类配体的性质已被确定为与植物鞘氨醇结合的生物碱喜树碱的衍生物。然而，其免疫原性的起源仍不清楚。
我们试图评估 Pru p 3 脂质配体在 Pru p 3 免疫原性中的作用。
使用不同细胞类型（单核细胞衍生的树突状细胞[moDCs]、外周血单核细胞[PBMCs]和上皮细胞和 iNKT-杂交瘤细胞系）的体外培养，通过测量细胞增殖、成熟标志物和细胞因子产生来确定配体的免疫能力。为了研究脂质配体在体内促进对普魯斯桃蛋白 3 致敏的能力，我们制备了桃过敏的小鼠模型，并分析了体液和嗜碱性粒细胞反应的变化。
Pru p 3 的脂质配体诱导 moDCs 的成熟和 PBMCs 的增殖。其免疫活性存在于配体的植物鞘氨醇尾部。该配体的佐剂活性也在体内得到了证实，其中 Pru p 3-配体复合物诱导的 IgE 水平高于单独的 Pru p 3。Pru p 3 配体的免疫能力由 CD1d 介导，因为 moDCs 的成熟被抗 CD1d 抗体抑制，并且 Pru p 3-配体与上皮细胞上的 CD1d 共定位。最后，由 CD1d 呈递的 Pru p 3 配体能够与 iNKTs 相互作用。
Pru p 3 脂质配体可以作为佐剂通过其与 CD1d 受体的识别来促进对 Pru p 3 的致敏。这种伴随脂质货物的固有佐剂活性可能是过敏现象背后机制的一般基本特征。
