华盛顿大学圣路易斯医学院Kenneth M. Murphy团队在研究中取得进展。他们发现了mRNA疫苗参与CD8⁺ T细胞启动的非常规途径。2026年4月15日出版的《自然》发表了这项成果。

在这里，该课题组研究人员报道mRNA-LNP疫苗不需要cDC1细胞或WDFY4依赖的交叉呈递途径来启动CD8⁺ T细胞，而是冗余地参与cDC1和cDC2细胞。而cDC1或cDC2单独启动的CD8⁺ T细胞表现出表型差异，两者都可以介导抗肿瘤反应和记忆形成。重要的是，cDCs从非造血细胞获得肽MHC-I复合物，称为异装，以依赖于I型干扰素的方式提供了CD8⁺ T细胞启动的重要组成部分。mRNA-LNP诱导的异装可能解释了它们激活CD8⁺ T细胞对抗疫苗未编码抗原的能力。

据悉，由mRNA和脂质纳米颗粒（LNPs）组成的疫苗通过诱导体内产生特异性蛋白抗原来激活B细胞和T细胞。B细胞可以直接被抗原激活，而T细胞的激活则需要MHC分子在特异性抗原呈递细胞（apc）上对抗原进行加工和呈递。在应对病毒感染、肿瘤以及基于蛋白质和dna的疫苗时，抗原向CD8⁺ T细胞的呈递特别依赖于1型常规树突状（cDC1）细胞，这种细胞专门用于外源抗原的高效交叉呈递。然而，类似的机制是否在mRNA-LNP疫苗接种中发挥作用尚不清楚。

附：英文原文

Title: mRNA vaccines engage unconventional pathways in CD8+ T cell priming

Author: Jo, Suin, Li, Lijin, Thakur, Chandrani, Telfer, Kevin A., Sultan, Hussein, Ohara, Ray A., He, Michelle, Nam, Giri, Chen, Jing, Ou, Feiya, Draghi, Monia, Valiante, Nicholas M., Schreiber, Robert D., Randolph, Gwendalyn J., Saligrama, Naresha, Murphy, Theresa L., Gillanders, William E., Murphy, Kenneth M.

Issue&Volume: 2026-04-15

Abstract: Vaccines composed of mRNA and lipid nanoparticles (LNPs) activate B cells and T cells by inducing in vivo production of specific protein antigens. While B cells can be activated directly by antigens, T cell activation requires antigen processing and presentation by MHC molecules on specialized antigen-presenting cells (APCs). In response to viral infections, tumours, and protein- and cDNA-based vaccines, antigen presentation to CD8+ T cells is particularly dependent on type 1 conventional dendritic (cDC1) cells, which are specialized for efficient cross-presentation of exogenous antigens1,2,3,4. However, whether similar mechanisms have a role in mRNA–LNP vaccination is unclear. Here we report that mRNA–LNP vaccines do not require cDC1 cells or the WDFY4-dependent cross-presentation pathway for CD8+ T cell priming but instead engage both cDC1 and cDC2 cells redundantly. While CD8+ T cells primed exclusively by either cDC1 or cDC2 cells showed phenotypic differences, both could mediate anti-tumour responses and memory formation. Importantly, acquisition by cDCs of peptide–MHC-I complexes from non-haematopoietic cells, called cross-dressing, provides a substantial component of CD8+ T cell priming, in a manner dependent on type I interferon. mRNA–LNP induction of cross-dressing might explain their ability to activate CD8+ T cells against antigens not encoded by the vaccine.

DOI: 10.1038/s41586-026-10353-6

Source: https://www.nature.com/articles/s41586-026-10353-6