Specific targeting of MR1-antigen complexes using nanobodies.

Nanobodies targeting MR1-5-OP-RU complexes effectively inhibit MAIT cell responses and enable T cell-mediated killing of infected and tumor cells.

• Why it matters: Targeting MR1-antigen complexes offers a promising approach for immune modulation, but the ability to generate specific antibodies has been unclear, limiting therapeutic development.
• What they did: Using yeast display technology, researchers developed high-affinity nanobodies that bind both mouse and human MR1-5-OP-RU, and engineered bispecific antibodies to redirect T cells for broad immune responses.
• The result: These nanobodies demonstrate in vitro and in vivo bioactivity, structural mimicry of TCRs, and enable targeted immune responses against bacterial infections and tumors, advancing immunotherapy strategies.