VA Portland Health Care System, Research and Development, 3710 SW US Veterans Hospital Road, Portland, 97239, Oregon, USA.
Pulmonary & Critical Care Medicine, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon, 97239, USA.
Sci Rep. 2019 Mar 18;9(1):4797. doi: 10.1038/s41598-019-41402-y.
The MHC-Ib molecule MR1 presents microbial metabolites to MR1-restricted T cells (MR1Ts). Given the ubiquitous expression of MR1 and the high prevalence of human MR1Ts, it is important to understand the mechanisms of MR1-dependent antigen presentation. Here, we show that MR1-dependent antigen presentation can be distinguished between intracellular Mycobacterium tuberculosis (Mtb) infection and exogenously added antigens. Although both Mtb infection and exogenously added antigens are presented by preformed MR1, only exogenously added antigens are capable of reusing MR1 that had been bound to the folic acid metabolite 6-formylpterin (6-FP). In addition, we identify an endosomal trafficking protein, Syntaxin 4, which is specifically involved in the presentation of exogenously delivered antigens but not Mtb-dependent antigen presentation. These data reveal there are multiple ways that MR1 can sample antigens and that MR1-mediated sampling of intracellular Mtb infection is distinguishable from the sampling of exogenously added antigens.
MHC-Ib 分子 MR1 可将微生物代谢产物呈递给 MR1 限制性 T 细胞 (MR1T)。鉴于 MR1 的广泛表达和人类 MR1T 的高流行率，了解 MR1 依赖性抗原呈递的机制非常重要。在这里，我们表明，MR1 依赖性抗原呈递可以区分细胞内结核分枝杆菌 (Mtb) 感染和外源添加的抗原。尽管 Mtb 感染和外源添加的抗原都由预先形成的 MR1 呈递，但只有外源添加的抗原才能重新利用与叶酸代谢物 6-甲酰基蝶呤 (6-FP) 结合的 MR1。此外，我们鉴定了一种内体运输蛋白Syntaxin 4，它特异性参与外源递呈的抗原呈递，但不参与 Mtb 依赖性抗原呈递。这些数据表明，MR1 可以通过多种方式取样抗原，并且 MR1 介导的细胞内 Mtb 感染的取样与外源添加抗原的取样不同。
