Baylor Institute for Immunology Research, 3434 Live Oak Street, Dallas, TX 75204, USA; Institute of Biomedical Studies, Baylor University, South 5th Street, Waco, TX 76706, USA.
Unité de Recherche sur les Maladies Infectieuses, Tropicales Emergentes, IRD 198, CNRS UMR7278, INSERM U1095, 27 bd Jean Moulin, 13385 Cedex 05, Marseille, France.
EBioMedicine. 2016 Jan 28;5:46-58. doi: 10.1016/j.ebiom.2016.01.029. eCollection 2016 Mar.
Dendritic cells (DCs) are major antigen-presenting cells that can efficiently prime and cross-prime antigen-specific T cells. Delivering antigen to DCs via surface receptors is thus an appealing strategy to evoke cellular immunity. Nonetheless, which DC surface receptor to target to yield the optimal CD8(+) and CD4(+) T cell responses remains elusive. Herein, we report the superiority of CD40 over 9 different lectins and scavenger receptors at evoking antigen-specific CD8(+) T cell responses. However, lectins (e.g., LOX-1 and Dectin-1) were more efficient than CD40 at eliciting CD4(+) T cell responses. Common and distinct patterns of subcellular and intracellular localization of receptor-bound αCD40, αLOX-1 and αDectin-1 further support their functional specialization at enhancing antigen presentation to either CD8(+) or CD4(+) T cells. Lastly, we demonstrate that antigen targeting to CD40 can evoke potent antigen-specific CD8(+) T cell responses in human CD40 transgenic mice. This study provides fundamental information for the rational design of vaccines against cancers and viral infections.
树突状细胞 (DCs) 是主要的抗原呈递细胞，能够有效地启动和交叉启动抗原特异性 T 细胞。因此，通过表面受体将抗原递呈给 DCs 是一种很有吸引力的策略，可以引发细胞免疫。尽管如此，针对哪种 DC 表面受体可以产生最佳的 CD8(+)和 CD4(+)T 细胞反应仍然难以捉摸。在此，我们报告了 CD40 优于 9 种不同的凝集素和清道夫受体诱导抗原特异性 CD8(+)T 细胞反应的优越性。然而，与 CD40 相比，凝集素（如 LOX-1 和 Dectin-1）更有效地诱导 CD4(+)T 细胞反应。受体结合的 αCD40、αLOX-1 和 αDectin-1 的亚细胞和细胞内定位的常见和独特模式进一步支持它们在增强抗原呈递给 CD8(+)或 CD4(+)T 细胞方面的功能专业化。最后，我们证明抗原靶向 CD40 可以在人类 CD40 转基因小鼠中引发强烈的抗原特异性 CD8(+)T 细胞反应。这项研究为针对癌症和病毒感染的疫苗的合理设计提供了基本信息。
