Specific targeting of MR1-antigen complexes using nanobodies.

Nanobodies targeting MR1-5-OP-RU complexes can bind both mouse and human MR1 and inhibit MAIT cell responses, demonstrating bioactivity in vitro and in vivo.

• Why it matters: Targeting MR1-antigen complexes offers a promising therapeutic approach due to MR1's limited polymorphism and conserved metabolite presentation, but the ability to generate specific antibodies remained uncertain.
• What they did: Using yeast display technology, researchers generated high-affinity nanobodies that bind MR1-5-OP-RU, solved their crystal structures, and engineered bispecific antibodies to redirect T cell killing of infected and tumor cells.
• The result: These nanobodies and bispecific antibodies enable immune redirection, broad T cell killing, and demonstrate potential for therapeutic applications against bacterial infections and tumors.