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

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...

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Published in:Communications biology 2024-02, Vol.7 (1), p.228-13, Article 228
Main Authors: Kulicke, Corinna A., Swarbrick, Gwendolyn M., Ladd, Nicole A., Cansler, Meghan, Null, Megan, Worley, Aneta, Lemon, Chance, Ahmed, Tania, Bennett, Joshua, Lust, Taylor N., Heisler, Chelsea M., Huber, Megan E., Krawic, Jason R., Ankley, Laurisa M., McBride, Savannah K., Tafesse, Fikadu G., Olive, Andrew J., Hildebrand, William H., Lewinsohn, Deborah A., Adams, Erin J., Lewinsohn, David M., Harriff, Melanie J.
Format: Article
Language:English
Subjects:
13/1
13/106
13/21
13/31
13/89
14/1
14/19
631/250/21
631/250/347
Antigen Presentation
Antigens - metabolism
Biomedical and Life Sciences
Cell activation
Histocompatibility Antigens Class I - metabolism
Life Sciences
Ligands
Lymphocyte Activation
Lymphocytes T
Monomers
Ribitol - analogs & derivatives
Uracil - analogs & derivatives
Wound healing
Wound infection
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Summary: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. Delivering MR1 ligand in the context of an MR1 monomer demonstrates transfer of this ligand onto cellular MR1. The stabilization of an inherently unstable ligand in the monomer has implications for antigen delivery and possibly vaccine design.
ISSN:2399-3642
2399-3642
DOI:10.1038/s42003-024-05912-4