The effect of MR1 ligand glyco-analogues on mucosal-associated invariant T (MAIT) cell activation.

摘要: Mucosal-associated invariant T (MAIT) cells are a subset of recently identified innate-like lymphocytes that appear to play an important role in many pathologies ranging from viral and bacterial infection, autoimmune disorders cancer. MAIT activated via the presentation ligands by MR1 on antigen presenting cell receptor (TCR), however few studies have explored effects systematic changes ligand structure binding activation. Herein, we report first study into sugar motif known agonists 7-hydroxy-6-methyl-8-D-ribityllumazine (RL-6-Me-7-OH) 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU). Tetramer staining revealed absence 2′-hydroxy group backbone lumazines improved MR1–MAIT TCR binding, which could be rationalised using computational docking studies. Although none cells, all 5-OP-RU analogues showed significant activation, with several exhibiting comparable activity 5-OP-RU. Docking different interactions between compared those observed for confirmed importance activity. Taken together, this information will assist development future potent antagonists cells.