近日，美国贝勒医学院Pavan Reddy团队开发出靶细胞上的MHC I类调节CD4⁺ T细胞介导的免疫。相关论文发表在2026年3月24日出版的《自然—免疫学》杂志上。

在这里，该课题组揭示了MHC I类在调节CD4⁺ T细胞介导的免疫中以前未被认识到的作用。在同种异体移植物抗宿主病和肿瘤模型中，该课题组人员证明靶细胞上MHC I类的缺失显著增加了它们对CD4⁺ T细胞毒性的易感性。转录组学和功能研究表明，这是由于靶细胞对铁下垂增强的敏感性增高所致。在大型人类转录组学和测序数据集中，CD4⁺ T细胞在黑色素瘤和MHC I类下调的错配修复缺陷结肠癌患者中增强免疫检查点阻断剂介导的应答中发挥了作用。这些发现修正并扩展了MHC I类在CD8⁺ T细胞和自然杀伤细胞免疫中的已知作用，并证明了它们在CD4⁺ T细胞介导的癌症和同种异体免疫中以前未被认识到的作用。

研究人员表示，主要组织相容性复合体（MHC） I类和II类分子分别向CD8⁺和CD4⁺ T细胞呈递抗原。

附：英文原文

Title: MHC class I on target cells regulates CD4+ T cell-mediated immunity

Author: Lauder, Emma, Gondal, Mahnoor, Wu, Meng-Chih, Yamamoto, Akira, Maneix, Laure, Zhao, Dongchang, Sun, Yaping, Cieslik, Marcin, Chinnaiyan, Arul M., Reddy, Pavan

Issue&Volume: 2026-03-24

Abstract: Major histocompatibility complex (MHC) class I and class II molecules present antigens to CD8+ and CD4+ T cells respectively. Here we uncover a previously unrecognized role for MHC class I in modulating CD4+ T cell-mediated immunity. In allogeneic graft-versus-host disease and tumor models, we demonstrate that the absence of MHC class I on target cells significantly increases their susceptibility to CD4+ T cell cytotoxicity. Transcriptomic and functional studies suggest that this was because of heightened sensitivity to enhanced ferroptosis of the target cells. In large human transcriptomic and sequencing datasets, a role for CD4+ T cells in enhancing immune checkpoint blocker-mediated responses in persons with melanoma and mismatch-repair-deficient colon cancers that have downregulated MHC class I was suggested. These findings revise and expand the known role of MHC class I in CD8+ T cell and natural killer cell immunity and demonstrate a previously unrecognized role in CD4+ T cell-mediated cancer and alloimmunity.

DOI: 10.1038/s41590-026-02480-z

Source: https://www.nature.com/articles/s41590-026-02480-z