抗原交叉呈递是树突状细胞和其他抗原呈递细胞进行协调细胞毒性响应以杀灭感染或癌细胞的重要机制。在此过程中，外源性抗原被树突状细胞内吞、处理，装载到MHC I类分子上，并呈递给CD8+ T细胞以激活它们。Sec22b是ER-Golgi中间室驻留的SNARE蛋白，与sintaxin4合作，协调运输相关的抗原处理蛋白和肽负载复合物到吞噬体，被蛋白水解后的抗原肽负载到MHC I类分子并被运输到细胞膜上。沉默树突状细胞原代培养及C57BL/6小鼠的树突状细胞中的Sec22b，严重影响了抗原交叉呈递，但对其他抗原呈递途径和细胞因子的产生和分泌均无影响。条件诱导沉默树突状细胞的Sec22b-/-小鼠显示出CD8+ T淋巴细胞引导不足，无法控制肿瘤生长，并对抗关卡免疫疗法具有抵抗力。在本研究中，我们表明Sec22b-/-小鼠在挑战亚致死剂量Trypanosoma cruzi trypomastigotes时呈现出特异性CD8+ T细胞反应不足，伴随血液寄生虫病增加和生存减少。版权所有© 2023 Biscari，Maza，Farré，Kaufman，Amigorena，Fresno，Gironès和Alloatti。

Antigen cross-presentation is a vital mechanism of dendritic cells and other antigen presenting cells to orchestrate the priming of cytotoxic responses towards killing of infected or cancer cells. In this process, exogenous antigens are internalized by dendritic cells, processed, loaded onto MHC class I molecules and presented to CD8+ T cells to activate them. Sec22b is an ER-Golgi Intermediate Compartment resident SNARE protein that, in partnership with sintaxin4, coordinates the recruitment of the transporter associated with antigen processing protein and the peptide loading complex to phagosomes, where antigenic peptides that have been proteolyzed in the cytosol are loaded in MHC class I molecules and transported to the cell membrane. The silencing of Sec22b in dendritic cells primary cultures and conditionally in dendritic cells of C57BL/6 mice, critically impairs antigen cross-presentation, but neither affects other antigen presentation routes nor cytokine production and secretion. Mice with Sec22b conditionally silenced in dendritic cells (Sec22b-/-) show deficient priming of CD8+ T lymphocytes, fail to control tumor growth, and are resistant to anti-checkpoint immunotherapy. In this work, we show that Sec22b-/- mice elicit a deficient specific CD8+ T cell response when challenged with sublethal doses of Trypanosoma cruzi trypomastigotes that is associated with increased blood parasitemia and diminished survival.Copyright © 2023 Biscari, Maza, Farré, Kaufman, Amigorena, Fresno, Gironès and Alloatti.