Wadehra Madhuri, Su Helen, Gordon Lynn K, Goodglick Lee, Braun Jonathan
Department of Pathology and Laboratory Medicine, University of California at Los Angeles, Los Angeles, CA 90095-1722, USA.
Clin Immunol. 2003 May;107(2):129-36. doi: 10.1016/s1521-6616(03)00048-2.
Dysregulation of class I major histocompatibility (MHC1) expression is an important mechanism of immunologic resistance for certain virus-infected or neoplastic cells. This study characterizes a new molecule affecting MHC1 expression and CTL cytotoxicity. Epithelial membrane protein 2 (EMP2) is a tetraspan protein recently identified for its role in suppressing B lymphoma tumorigenicity. The biochemistry of EMP2 suggests that it regulates the surface expression of certain membrane proteins, notably those destined for lipid raft microdomains. In this study, retroviral overexpression of EMP2 in target cells increased their susceptibility to CTL cytotoxicity. Conversely, down-expression of EMP2 using an EMP2-specific ribozyme rendered target cells CTL-resistant. EMP2 expression increased the surface levels of MHC1, CD54, and GM1 glycolipids. Biochemical fractionation indicated that these molecules reside with EMP2 in a lipid raft membrane compartment. Among MHC1 proteins, surface display of H-2D was particularly dependent on EMP2 expression, and blocking antibodies demonstrated that H-2D was critical for allogeneic CTL recognition. This study demonstrates an unexpected role for a tetraspan protein in CTL-mediated cell death and MHC1 surface trafficking.
I类主要组织相容性复合体（MHC1）表达失调是某些病毒感染细胞或肿瘤细胞产生免疫抗性的重要机制。本研究对一种影响MHC1表达和CTL细胞毒性的新分子进行了表征。上皮膜蛋白2（EMP2）是一种四跨膜蛋白，最近因其在抑制B淋巴瘤致瘤性中的作用而被发现。EMP2的生物化学性质表明它可调节某些膜蛋白的表面表达，尤其是那些定位于脂筏微结构域的蛋白。在本研究中，靶细胞中EMP2的逆转录病毒过表达增加了它们对CTL细胞毒性的敏感性。相反，使用EMP2特异性核酶下调EMP2表达使靶细胞对CTL产生抗性。EMP2表达增加了MHC1、CD54和GM1糖脂的表面水平。生化分级分离表明这些分子与EMP2共存在脂筏膜区室中。在MHC1蛋白中，H-2D的表面展示尤其依赖于EMP2表达，阻断抗体表明H-2D对同种异体CTL识别至关重要。本研究证明了一种四跨膜蛋白在CTL介导的细胞死亡和MHC1表面转运中具有意想不到的作用。
