科利毒素，一种早期且神秘的癌症（免疫）治疗方法，是基于链球菌（Streptococcus pyogenes）制备的。作为探索具有免疫调节潜力的细菌代谢物的一部分，我们在细胞免疫测定中检测了S. pyogenes的代谢物，并鉴定出了一种单一的膜脂质——18:1/18:0/18:1/18:0磷脂。我们进一步在其他细胞测定中对其活性进行了分析，结果显示它是TLR2-TLR1信号通路的激动剂，具有6 μM的EC50和强效的TNF-α诱导作用。在免疫测定中，一个具有换位酰链的合成类似物没有可测的活性。鉴定出结构活性受限的单一免疫原性磷脂对于免疫调节、癌症免疫治疗和链球菌后自身免疫性疾病具有重要意义。

Coley's toxins, an early and enigmatic form of cancer (immuno)therapy, were based on preparations of Streptococcus pyogenes. As part of a program to explore bacterial metabolites with immunomodulatory potential, S. pyogenes metabolites were assayed in a cell-based immune assay, and a single membrane lipid, 18:1/18:0/18:1/18:0 cardiolipin, was identified. Its activity was profiled in additional cellular assays, which showed it to be an agonist of a TLR2-TLR1 signaling pathway with a 6 μM EC50 and robust TNF-α induction. A synthetic analog with switched acyl chains had no measurable activity in immune assays. The identification of a single immunogenic cardiolipin with a restricted structure-activity profile has implications for immune regulation, cancer immunotherapy, and poststreptococcal autoimmune diseases.