Delivery of loaded MR1 monomer results in efficient ligand exchange to host MR1 and subsequent MR1T cell activation

Autor: Corinna A. Kulicke, Gwendolyn M. Swarbrick, Nicole A. Ladd, Meghan Cansler, Megan Null, Aneta Worley, Chance Lemon, Tania Ahmed, Joshua Bennett, Taylor N. Lust, Chelsea M. Heisler, Megan E. Huber, Jason R. Krawic, Laurisa M. Ankley, Savannah K. McBride, Fikadu G. Tafesse, Andrew J. Olive, William H. Hildebrand, Deborah A. Lewinsohn, Erin J. Adams, David M. Lewinsohn, Melanie J. Harriff
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Communications Biology, Vol 7, Iss 1, Pp 1-13 (2024)
Druh dokumentu: article
ISSN: 2399-3642
DOI: 10.1038/s42003-024-05912-4
Popis: Abstract 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.
Databáze: Directory of Open Access Journals
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