Disclosed herein are immunostimulatory oligonucleotides and compositions and methods of use thereof. More specifically, immunostimulatory oligonucleotides, methods of optimizing the immunostimulatory properties of oligonucleotides, and methods of using the immunostimulatory oligonucleotides to elicit a toll-like receptor 21 (TLR21)-mediated immune response are disclosed.本文揭示免疫刺激性寡核苷酸以及其組成物與使用方法。更具體而言,揭示免疫刺激性寡核苷酸、優化該等寡核苷酸之免疫刺激性性質的方法以及使用該等免疫刺激性寡核苷酸來引起類鐸受體21(TLR21)媒介之免疫反應的方法。