Hartman Mor-Li, Lin Shih-Yao, Jouvin Marie-Hélène, Kinet Jean-Pierre
Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115, USA.
Mol Immunol. 2008 Apr;45(8):2307-11. doi: 10.1016/j.molimm.2007.11.017. Epub 2008 Jan 7.
The high affinity receptor for immunoglobulin E, Fc epsilon RI, is a critical component of IgE-mediated allergic reactions. It is expressed as a tetramer (alphabetagamma(2)) made of an IgE-binding alpha chain and a signaling module formed by the beta chain and a dimer of gamma chains. It is expressed in humans and rodents on basophils and mast cells at a high level, and, upon activation, it induces the liberation of allergy mediators. In humans a trimeric form lacking the beta chain also exists (alphagamma(2)). This trimeric form is expressed on antigen presenting cells where it acts to facilitate antigen presentation via IgE. Both the expression and the signaling capacity of the trimer are lower than those of the tetramer. The differences between human (tetrameric and trimeric) and murine (tetrameric only) expression is explained in part by the fact that mouse alpha cannot be expressed at the cell surface in the absence of beta, while human alpha can. Here we demonstrate that the capacity of human alpha to be expressed at the cell surface in the absence of beta is encoded entirely in its extracellular domain. These findings show that the extracellular domain of the type I transmembrane protein Fc epsilon RI alpha plays a role in Fc epsilon RI intracellular processing and expression at the cell surface.
免疫球蛋白E的高亲和力受体FcεRI是IgE介导的过敏反应的关键组成部分。它以四聚体（αβγ₂）的形式表达，由一条IgE结合α链和一个由β链及γ链二聚体形成的信号模块组成。它在人类和啮齿动物的嗜碱性粒细胞和肥大细胞上高水平表达，激活后可诱导过敏介质的释放。在人类中还存在一种缺少β链的三聚体形式（αγ₂）。这种三聚体形式在抗原呈递细胞上表达，通过IgE促进抗原呈递。三聚体的表达和信号传导能力均低于四聚体。人类（四聚体和三聚体）与小鼠（仅四聚体）表达的差异部分是由于在没有β链的情况下，小鼠α链无法在细胞表面表达，而人类α链可以。在此我们证明，人类α链在没有β链时在细胞表面表达的能力完全由其胞外结构域编码。这些发现表明，I型跨膜蛋白FcεRIα的胞外结构域在FcεRI的细胞内加工及在细胞表面的表达中发挥作用。
