High-throughput isolation and characterization of anti-miHA TCRs
Ito S, Martin E, Panousis C, et al. High Throughput Cloning Reveals Diverse Properties of T Cell Receptors Targeting Minor Histocompatibility Antigens. Blood Advances. 2025; (doi: 10.1182/bloodadvances.2025017680).
An innovative high-throughput platform that allows important T cell receptors (TCRs) to be cloned at a rapid pace could help scientists better understand the mechanics of minor histocompatibility antigens (miHAs) in the setting of allogeneic stem cell transplantation (allo-HSCT). The novel system, which works without the usual complexity and cost of approaches such as nucleic acid sequencing or gene synthesis, reproduces TCRs that use CD8 cells to detect human miHAs. The study authors cloned dozens of unique TCRs recognizing HA-1 and HA-2, including several from the blood of an HLA-A*02:01 HA-1R/R patient who was immunized against HA-1H while pregnant and several more from HA-2V-tetramer-positive cells from a patient relapsing with myelodysplastic syndrome after allo-HSCT. Investigators say the research underscores the viability of the high-throughput cloning platform, which offers a new technique with broad application potential for isolating and characterizing TCRs.