Kraft Stefan, Rana Shalini, Jouvin Marie-Hélène, Kinet Jean-Pierre
Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.
Int Arch Allergy Immunol. 2004 Sep;135(1):62-72. doi: 10.1159/000080231. Epub 2004 Aug 13.
The high affinity receptor for IgE, FcepsilonRI, is a multimeric surface receptor that is expressed exclusively as a tetramer on rodent cells, but exists as a tetramer or trimer on human cells. The tetrameric form is expressed on effector cells of allergic responses such as mast cells and basophils and is composed of an IgE-binding alpha-subunit, a beta-subunit and a gamma-subunit dimer. Complexes lacking the beta-subunit are found on human antigen-presenting cells. On mast cells and basophils, FcepsilonRI is essential for IgE-mediated acute allergic reactions. Crosslinking of FcepsilonRI by IgE and multivalent antigen induces a signaling cascade that culminates in the release of preformed mediators and the synthesis of lipid mediators and cytokines. The beta-subunit functions as an amplifier of FcepsilonRI expression and signaling. As a consequence, strongly enhanced mast cell effector functions and in vivo allergic reactions can be observed in the presence of FcepsilonRIbeta. In contrast, a truncated beta-isoform (betaT) that is produced by alternative splicing acts as an inhibitor of FcepsilonRI surface expression. Thus, by producing two proteins with antagonistic functions, the FcepsilonRIbeta gene could serve as a potent regulator of allergic responses. In addition, the genomic region encompassing the beta-chain has been linked to atopy and a number of polymorphisms within the FcepsilonRIbeta gene are associated with various atopic diseases. It remains to be elucidated how these polymorphisms might affect the allergic phenotype. These functions of the beta-chain together with the described genetic linkages to atopy make it a candidate for a role in the pathophysiology of allergic diseases.
IgE的高亲和力受体FcepsilonRI是一种多聚体表面受体，在啮齿动物细胞上仅以四聚体形式表达，但在人类细胞上则以四聚体或三聚体形式存在。四聚体形式在过敏反应的效应细胞如肥大细胞和嗜碱性粒细胞上表达，由一个IgE结合α亚基、一个β亚基和一个γ亚基二聚体组成。缺乏β亚基的复合物存在于人类抗原呈递细胞上。在肥大细胞和嗜碱性粒细胞上，FcepsilonRI对于IgE介导的急性过敏反应至关重要。IgE和多价抗原使FcepsilonRI交联会诱导信号级联反应，最终导致预形成介质的释放以及脂质介质和细胞因子的合成。β亚基作为FcepsilonRI表达和信号传导的放大器。因此，在存在FcepsilonRIβ的情况下，可以观察到肥大细胞效应功能和体内过敏反应的强烈增强。相比之下，由可变剪接产生的截短β异构体（βT）作为FcepsilonRI表面表达的抑制剂。因此，通过产生两种具有拮抗功能的蛋白质，FcepsilonRIβ基因可以作为过敏反应的有效调节剂。此外，包含β链的基因组区域已与特应性相关联，并且FcepsilonRIβ基因内的一些多态性与各种特应性疾病相关。这些多态性如何影响过敏表型仍有待阐明。β链的这些功能以及所描述的与特应性的遗传联系使其成为过敏性疾病病理生理学中发挥作用的候选者。
