Integrated Department of Immunology, National Jewish Health & University of Colorado School of Medicine, Denver, CO 80206, USA.
Immunol Res. 2013 Mar;55(1-3):83-90. doi: 10.1007/s12026-012-8351-1.
Metal hypersensitivity is a common immune disorder. Human immune systems mount the allergic attacks on metal ions through skin contacts, lung inhalation and metal-containing artificial body implants. The consequences can be simple annoyances to life-threatening systemic illness. Allergic hyper-reactivities to nickel (Ni) and beryllium (Be) are the best-studied human metal hypersensitivities. Ni-contact dermatitis affects 10 % of the human population, whereas Be compounds are the culprits of chronic Be disease (CBD). αβ T cells (T cells) play a crucial role in these hypersensitivity reactions. Metal ions work as haptens and bind to the surface of major histocompatibility complex (MHC) and peptide complex. This modifies the binding surface of MHC and triggers the immune response of T cells. Metal-specific αβ T cell receptors (TCRs) are usually MHC restricted, especially MHC class II (MHCII) restricted. Numerous models have been proposed, yet the mechanisms and molecular basis of metal hypersensitivity remain elusive. Recently, we determined the crystal structures of the Ni and Be presenting human MHCII molecules, HLA-DR52c (DRA0101, DRB30301) and HLA-DP2 (DPA10103, DPB10201). These structures revealed unusual features of MHCII molecules and shed light on how metal ions are recognized by T cells.
金属过敏是一种常见的免疫紊乱。人类免疫系统通过皮肤接触、肺部吸入和含金属的人工植入物来引发对金属离子的过敏反应。其后果从简单的生活困扰到威胁生命的全身性疾病都有。镍（Ni）和铍（Be）过敏反应是研究最充分的人类金属过敏症。镍接触性皮炎影响了 10%的人口，而铍化合物是慢性铍病（CBD）的罪魁祸首。αβ T 细胞（T 细胞）在这些过敏反应中起着至关重要的作用。金属离子作为半抗原与主要组织相容性复合体（MHC）和肽复合物结合。这改变了 MHC 的结合表面，并引发了 T 细胞的免疫反应。金属特异性的 αβ T 细胞受体（TCR）通常受 MHC 限制，尤其是 MHC Ⅱ类（MHCII）限制。已经提出了许多模型，但金属过敏的机制和分子基础仍然难以捉摸。最近，我们确定了 Ni 和 Be 呈递的人类 MHCII 分子 HLA-DR52c（DRA0101、DRB30301）和 HLA-DP2（DPA10103、DPB10201）的晶体结构。这些结构揭示了 MHCII 分子的一些不寻常特征，并阐明了金属离子如何被 T 细胞识别。
