Division of Pulmonary, Allergy, and Critical Care Medicine, Oregon Health & Science University, Portland, OR, 97239, USA.
Division of Infectious Diseases, Department of Pediatrics, Oregon Health & Science University, Portland, OR, 97239, USA.
Commun Biol. 2024 Feb 24;7(1):228. doi: 10.1038/s42003-024-05912-4.
MR1-restricted T cells have been implicated in microbial infections, sterile inflammation, wound healing and cancer. Similar to other antigen presentation molecules, evidence supports multiple, complementary MR1 antigen presentation pathways. To investigate ligand exchange pathways for MR1, we used MR1 monomers and tetramers loaded with 5-(2-oxopropylideneamino)-6-d-ribitylaminouracil (5-OP-RU) to deliver the antigen. Using MR1-deficient cells reconstituted with wild-type MR1 or MR1 molecules that cannot bind 5-OP-RU, we show that presentation of monomer-delivered 5-OP-RU is dependent on cellular MR1 and requires the transfer of ligand from the soluble molecule onto MR1 expressed by the antigen presenting cell. This mode of antigen delivery strengthens the evidence for post-ER ligand exchange pathways for MR1, which could represent an important avenue by which MR1 acquires antigens derived from endocytosed pathogens.
MR1 限制的 T 细胞已被牵涉到微生物感染、无菌性炎症、伤口愈合和癌症中。与其他抗原呈递分子相似，有证据支持多种互补的 MR1 抗原呈递途径。为了研究 MR1 的配体交换途径，我们使用装载有 5-(2-氧代丙二酰氨基)-6-d-核糖基尿嘧啶（5-OP-RU）的 MR1 单体和四聚体来递呈抗原。使用用野生型 MR1 或不能结合 5-OP-RU 的 MR1 分子重建的 MR1 缺陷细胞，我们表明单体递呈的 5-OP-RU 的呈递依赖于细胞表面的 MR1，并需要配体从可溶性分子转移到抗原呈递细胞上表达的 MR1。这种抗原递呈方式加强了 MR1 的 ER 后配体交换途径的证据，这可能是 MR1 获得内吞病原体衍生抗原的重要途径。
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