Specific targeting of MR1-antigen complexes using nanobodies.

Hisham S Hussain; Samuel J Redmond; Wael Awad; Calvin Xu; Caroline Soliman; Huimeng Wang; Yuyang Zhang; Lisa Ciacchi; Alexis P Gonzalez; Jeffrey YW Mak; David P Fairlie; James McCluskey; Alexandra J Corbett; Adam P Uldrich; Jamie Rossjohn; Dale I Godfrey; Hui-Fern Koay; Nicholas A Gherardin

Journal article

Specific targeting of MR1-antigen complexes using nanobodies.

Hisham S Hussain, Samuel J Redmond, Wael Awad, Calvin Xu, Caroline Soliman, Huimeng Wang, Yuyang Zhang, Lisa Ciacchi, Alexis P Gonzalez, Jeffrey YW Mak, David P Fairlie, James McCluskey, Alexandra J Corbett, Adam P Uldrich, Jamie Rossjohn, Dale I Godfrey, Hui-Fern Koay, Nicholas A Gherardin

Sci Immunol | American Association for the Advancement of Science (AAAS) | Published : 2026

DOI: 10.1126/sciimmunol.aeb8726

Abstract

T cell receptor mimic (TCRm) antibodies that bind peptide-human leukocyte antigen complexes have great therapeutic potential. Major histocompatibility complex class I-related protein 1 (MR1) exhibits limited polymorphism and presents conserved metabolites, such as 5-OP-RU, derived from microbial riboflavin biosynthesis. Whether antibodies targeting such MR1-5-OP-RU complexes can be generated remains unclear. Using yeast display technology, nanobodies with high affinity toward the MR1-5-OP-RU complex were generated. These nanobodies can bind both mouse and human MR1-5-OP-RU and inhibit mucosal-associated invariant T (MAIT) cell responses to 5-OP-RU and bacterial challenge, demonstrating in vi..

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