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

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

doi:10.1038/s42003-024-05912-4

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

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. AdamsDavid M. Lewinsohn, Melanie J. Harriff

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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.

Original language	English (US)
Article number	228
Journal	Communications Biology
Volume	7
Issue number	1
DOIs	https://doi.org/10.1038/s42003-024-05912-4
State	Published - Dec 2024

ASJC Scopus subject areas

Medicine (miscellaneous)
General Biochemistry, Genetics and Molecular Biology
General Agricultural and Biological Sciences

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Kulicke, C. A., Swarbrick, G. M., Ladd, N. A., Cansler, M., Null, M., Worley, A., Lemon, C., Ahmed, T., Bennett, J., Lust, T. N., Heisler, C. M., Huber, M. E., Krawic, J. R., Ankley, L. M., McBride, S. K., Tafesse, F. G., Olive, A. J., Hildebrand, W. H., Lewinsohn, D. A., ... Harriff, M. J. (2024). Delivery of loaded MR1 monomer results in efficient ligand exchange to host MR1 and subsequent MR1T cell activation. Communications Biology, 7(1), Article 228. https://doi.org/10.1038/s42003-024-05912-4

Kulicke, CA, Swarbrick, GM, Ladd, NA, Cansler, M, Null, M, Worley, A, Lemon, C, Ahmed, T, Bennett, J, Lust, TN, Heisler, CM, Huber, ME, Krawic, JR, Ankley, LM, McBride, SK, Tafesse, FG, Olive, AJ, Hildebrand, WH, Lewinsohn, DA, Adams, EJ, Lewinsohn, DM & Harriff, MJ 2024, 'Delivery of loaded MR1 monomer results in efficient ligand exchange to host MR1 and subsequent MR1T cell activation', Communications Biology, vol. 7, no. 1, 228. https://doi.org/10.1038/s42003-024-05912-4

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

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.",

author = "Kulicke, {Corinna A.} and Swarbrick, {Gwendolyn M.} and Ladd, {Nicole A.} and Meghan Cansler and Megan Null and Aneta Worley and Chance Lemon and Tania Ahmed and Joshua Bennett and Lust, {Taylor N.} and Heisler, {Chelsea M.} and Huber, {Megan E.} and Krawic, {Jason R.} and Ankley, {Laurisa M.} and McBride, {Savannah K.} and Tafesse, {Fikadu G.} and Olive, {Andrew J.} and Hildebrand, {William H.} and Lewinsohn, {Deborah A.} and Adams, {Erin J.} and Lewinsohn, {David M.} and Harriff, {Melanie J.}",

note = "Publisher Copyright: {\textcopyright} This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2024.",

year = "2024",

month = dec,

doi = "10.1038/s42003-024-05912-4",

language = "English (US)",

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AU - Kulicke, Corinna A.

AU - Swarbrick, Gwendolyn M.

AU - Ladd, Nicole A.

AU - Cansler, Meghan

AU - Null, Megan

AU - Worley, Aneta

AU - Lemon, Chance

AU - Ahmed, Tania

AU - Bennett, Joshua

AU - Lust, Taylor N.

AU - Heisler, Chelsea M.

AU - Huber, Megan E.

AU - Krawic, Jason R.

AU - Ankley, Laurisa M.

AU - McBride, Savannah K.

AU - Tafesse, Fikadu G.

AU - Olive, Andrew J.

AU - Hildebrand, William H.

AU - Lewinsohn, Deborah A.

AU - Adams, Erin J.

AU - Lewinsohn, David M.

AU - Harriff, Melanie J.

PY - 2024/12

Y1 - 2024/12

N2 - 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.

AB - 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.

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

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