DataSheet_1_Palladium-Induced Temporal Internalization of MHC Class I Contributes to T Cell-Mediated Antigenicity.pdf

Palladium (Pd) is a widely used metal and extremely important biomaterial for the reconstruction of occlusions during dental restorations. However, metallic biomaterials can cause serious allergic reactions, such as Pd-related oral mucositis seen in dentistry. Metal allergy is categorized as a type IV allergy and we demonstrated that CD8 T cells play an important role in Pd allergy previously. As TCR of CD8 T cells recognizes MHC class I/peptide complex, the antigen specificity to this complex seems to be generated during Pd allergy. However, it remains unknown if Pd affects the MHC class I/peptide complex. In this study, we investigated the behavior of the MHC class I/peptide complex in response to Pd treatment. We found that PdCl2 treatment altered peptide presentation on MHC class I and that co-culture with Pd-treated DC2.4 cells induced activation of Pd-responsive TCR-expressing T cell line. Furthermore, PdCl2 treatment induced temporal MHC class I internalization and inhibition of membrane movement suppressed Pd-induced T cell-mediated antigenicity. These data suggest that Pd-induced MHC class I internalization is critical for generation of antigenicity through a mechanism including differential peptide loading on MHC class I, which results in Pd allergy.

钯（Pd）是一种应用广泛的金属，亦是牙科修复术中咬合重建领域极为重要的生物材料。然而，金属生物材料可引发严重过敏反应，例如牙科临床中所见的钯相关性口腔黏膜炎。金属过敏属于IV型超敏反应，既往研究已证实CD8 T细胞在钯过敏过程中发挥关键作用。由于CD8 T细胞的T细胞受体（TCR）可识别主要组织相容性复合体I类（MHC I）/肽复合物，该复合物的抗原特异性似乎在钯过敏进程中产生。但目前尚不清楚钯是否会对MHC I/肽复合物产生影响。本研究探讨了MHC I/肽复合物在钯处理后的行为变化。研究发现，氯化钯（PdCl2）处理可改变MHC I分子上的肽提呈；且与经钯处理的DC2.4细胞共培养，可诱导表达钯应答性TCR的T细胞系激活。此外，氯化钯处理可诱导MHC I发生暂时性内吞，且抑制膜运动可阻断钯诱导的T细胞介导的抗原性。上述数据表明，钯诱导的MHC I内吞对抗原性的产生至关重要，其机制涉及MHC I分子上的差异化肽负载，最终引发钯过敏。