Barrera-Avalos Carlos, Briceño Pedro, Valdés Daniel, Imarai Mónica, Leiva-Salcedo Elías, Rojo Leonel E, Milla Luis A, Huidobro-Toro Juan Pablo, Robles-Planells Claudia, Escobar Alejandro, Di Virgilio Francesco, Morón Gabriel, Sauma Daniela, Acuña-Castillo Claudio
Departamento de Biología, Facultad de Química y Biología, Universidad de Santiago de Chile, USACH, Alameda, Santiago 3363, Chile.
Centro de Biotecnología Acuícola, Universidad de Santiago de Chile, USACH, Alameda 3363 Santiago, Chile.
iScience. 2021 Nov 26;24(12):103520. doi: 10.1016/j.isci.2021.103520. eCollection 2021 Dec 17.
T cell activation requires the processing and presentation of antigenic peptides in the context of a major histocompatibility complex (MHC complex). Cross-dressing is a non-conventional antigen presentation mechanism, involving the transfer of preformed peptide/MHC complexes from whole cells, such as apoptotic cells (ACs) to the cell membrane of professional antigen-presenting cells (APCs), such as dendritic cells (DCs). This is an essential mechanism for the induction of immune response against viral antigens, tumors, and graft rejection, which until now has not been clarified. Here we show for first time that the P2X7 receptor (P2X7R) is crucial to induce cross-dressing between ACs and Bone-Marrow DCs (BMDCs). In controlled assays, we found that the P2X7R in both ACs and BMDCs is required to induce membrane and fully functional peptide/MHC complex transfer to BMDCs. These findings show that acquisition of ACs-derived preformed antigen/MHC-I complexes by BMDCs requires P2X7R expression.
T细胞活化需要在主要组织相容性复合体（MHC复合体）的背景下对抗原肽进行加工和呈递。交叉呈递是一种非常规的抗原呈递机制，涉及将预先形成的肽/MHC复合体从全细胞，如凋亡细胞（ACs）转移到专职抗原呈递细胞（APCs）的细胞膜上，如树突状细胞（DCs）。这是诱导针对病毒抗原、肿瘤和移植排斥反应的免疫应答的一种重要机制，迄今为止尚未阐明。在此，我们首次表明P2X7受体（P2X7R）对于诱导ACs和骨髓来源的树突状细胞（BMDCs）之间的交叉呈递至关重要。在对照实验中，我们发现ACs和BMDCs中的P2X7R对于诱导膜和功能完整的肽/MHC复合体转移至BMDCs是必需的。这些发现表明，BMDCs获取ACs来源的预先形成的抗原/MHC-I复合体需要P2X7R的表达。
