不变T细胞受体而非CD1d决定了C-糖苷类似物对人源与鼠源不变自然杀伤T细胞的优先活性。

Invariant TCR rather than CD1d shapes the preferential activities of C-glycoside analogues against human versus murine invariant NKT cells.

作者信息

Li Xiangming, Shiratsuchi Takayuki, Chen Guangwu, Dellabona Paolo, Casorati Giulia, Franck Richard W, Tsuji Moriya

机构信息

HIV and Malaria Vaccine Program, Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY 10016, USA.

出版信息

J Immunol. 2009 Oct 1;183(7):4415-21. doi: 10.4049/jimmunol.0901021. Epub 2009 Sep 4.

DOI:10.4049/jimmunol.0901021

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3603359/

Abstract

C-glycoside analogues of alpha-galactosylceramide were shown to activate both human and mouse invariant NKT (iNKT) cells. Among these analogues, GCK152, which has an aromatic ring in the acyl chain, exhibited a stronger stimulatory activity against human iNKT cells and a much weaker activity against murine iNKT cells than GCK127 that has an almost identical fatty acyl chain as alpha-galactosylceramide. In this study, we have found that invariant TCR (invTCR) expressed by iNKT cells, but not CD1d expressed by APCs, command the species-specific preferential activity of C-glycosides, and that their preferential activity against human vs murine iNKT cells correlate with the binding affinity of glycolipid-CD1d complex to invTCR of respective iNKT cells rather than that of glycolipid to human or murine CD1d molecules. Overall, the structural difference of invTCR appears to supersede those of CD1d molecule in shaping the strength of the biological activity of C-glycoside analogues.

摘要

α-半乳糖神经酰胺的C-糖苷类似物被证明可激活人和小鼠的不变自然杀伤T（iNKT）细胞。在这些类似物中，在酰基链中具有芳香环的GCK152对人iNKT细胞表现出更强的刺激活性，而对鼠iNKT细胞的活性比对具有与α-半乳糖神经酰胺几乎相同脂肪酰基链的GCK127弱得多。在本研究中，我们发现iNKT细胞表达的不变T细胞受体（invTCR）而非抗原呈递细胞（APC）表达的CD1d决定了C-糖苷的物种特异性优先活性，并且它们对人iNKT细胞与鼠iNKT细胞的优先活性与糖脂-CD1d复合物对各自iNKT细胞的invTCR的结合亲和力相关，而非与糖脂对人或鼠CD1d分子的结合亲和力相关。总体而言，在塑造C-糖苷类似物生物活性强度方面，invTCR的结构差异似乎比CD1d分子的结构差异更具决定性。