Recombinant MHC molecules displaying single peptides in their peptide binding cleft are valuable reagents for identifying T cells that bind specific peptide-MHC complexes or for analyzing binding properties of soluble T cell receptors or bispecific T cell receptors. Without peptide ligands, MHC complexes are unstable and decay quickly, making the production of soluble monomers for analytical purposes labor intensive.
In this week’s issue of Science Immunology, Immatics scientists and collaborators present functionally empty and peptide-receptive HLA-A*02:01 molecules, developed in the Springer lab at the Jacobs University Bremen, that represent a cutting-edge solution to this problem: The engineered molecule can be produced in advance without peptide but forms peptide-MHC complexes within minutes after adding peptides of choice in a one-step loading procedure.
Using this molecule, Immatics' scientists can quickly generate large libraries of peptide-MHC complexes. In the research article, they demonstrate one potential application of such libraries as part of a high-throughput screening platform for affinity-maturated TCRs that allows quick and in-depth characterization of their binding behaviour.
Read the full article here.