PDF(Pubmed)
Abstract：
Mucosal-associated invariant T (MAIT) cells are a subset of unconventional T cells that recognize small molecule metabolites presented by major histocompatibility complex class I related protein 1 (MR1), via an αβ T cell receptor (TCR). MAIT TCRs feature an essentially invariant TCR α-chain, which is highly conserved between mammals. Similarly, MR1 is the most highly conserved major histocompatibility complex-I-like molecule. This extreme conservation, including the mode of interaction between the MAIT TCR and MR1, has been shown to allow for species-mismatched reactivities unique in T cell biology, thereby allowing the use of selected species-mismatched MR1-antigen (MR1-Ag) tetramers in comparative immunology studies. However, the pattern of cross-reactivity of species-mismatched MR1-Ag tetramers in identifying MAIT cells in diverse species has not been formally assessed. We developed novel cattle and pig MR1-Ag tetramers and utilized these alongside previously developed human, mouse, and pig-tailed macaque MR1-Ag tetramers to characterize cross-species tetramer reactivities. MR1-Ag tetramers from each species identified T cell populations in distantly related species with specificity that was comparable to species-matched MR1-Ag tetramers. However, there were subtle differences in staining characteristics with practical implications for the accurate identification of MAIT cells. Pig MR1 is sufficiently conserved across species that pig MR1-Ag tetramers identified MAIT cells from the other species. However, MAIT cells in pigs were at the limits of phenotypic detection. In the absence of sheep MR1-Ag tetramers, a MAIT cell population in sheep blood was identified phenotypically, utilizing species-mismatched MR1-Ag tetramers. Collectively, our results validate the use and define the limitations of species-mismatched MR1-Ag tetramers in comparative immunology studies.
摘要：
粘膜相关的不变T（MAIT）细胞是一组非常规T细胞，可识别MHC-I相关蛋白1（MR1）呈递的小分子代谢物，通过αβT细胞受体（TCR）。MAITTCR具有基本上不变的TCRα链，这在哺乳动物之间是高度保守的。同样，MR1是最高度保守的MHC-I样分子。这种极端的保护，包括MAITTCR和MR1之间的相互作用模式，已显示允许T细胞生物学中独特的物种错配反应性，从而允许在比较免疫学研究中使用选定的物种错配MR1抗原（MR1-Ag）四聚体。然而,物种错配MR1-Ag四聚体在鉴定不同物种MAIT细胞时的交叉反应模式尚未得到正式评估.我们开发了新的牛和猪MR1-Ag四聚体，并利用这些与先前开发的人类，小鼠和猪尾猕猴MR1-Ag四聚体表征跨物种四聚体反应性。来自每个物种的MR1-Ag四聚体以与物种匹配的MR1-Ag四聚体相当的特异性鉴定了远亲物种中的T细胞群体。然而,染色特征存在细微差异，对MAIT细胞的准确鉴定具有实际意义。猪MR1在物种中充分保守，猪MR1-Ag四聚体鉴定了来自其他物种的MAIT细胞。然而,猪的MAIT细胞处于表型检测的极限。在没有绵羊MR1-Ag四聚体的情况下，通过表型鉴定了绵羊血液中的MAIT细胞群，利用物种错配的MR1-Ag四聚体。总的来说，我们的结果验证了物种错配MR1-Ag四聚体在比较免疫学研究中的用途和局限性.
