Recombinant Binding Proteins for Peptide-MHC Complexes

The binding protein is divided into two distinct functional domains: a pMHC-binding domain (such as a DARPin or antibody fragment) that provides high-affinity binding, and a T-cell engaging domain (such as an anti-CD3 antibody) that ensures specific T-cell activation. This segmentation allows each domain to perform its specialized function independently, achieving both high affinity and high specificity without the cross-reactivity problems of affinity-enhanced TCRs.

The invention uses self-service by employing in silico peptide elution methods and phage display technology to automatically identify and select pMHC-specific binders from large libraries without requiring animal immunization and manual screening of hundreds of clones. The computational peptide elution predicts which peptides are presented by target pMHC complexes, and phage display libraries are screened based on these predictions, dramatically increasing isolation efficiency while maintaining high specificity.

The invention applies preliminary action by using in silico peptide elution to pre-identify the specific peptides presented by target pMHC complexes before conducting phage display screening. This preliminary computational step guides the selection of phage clones that are most likely to bind the target pMHC, enabling the isolation of high-affinity binders in fewer screening rounds and without requiring affinity maturation procedures.

The invention replaces mechanical and labor-intensive procedures with computational methods. In silico peptide elution algorithms predict pMHC-bound peptides in silico, replacing the need for complex experimental peptide screening. Phage display screening is guided by computational predictions, replacing random screening approaches. This substitution of computational methods for mechanical procedures dramatically reduces development complexity while maintaining high binding affinity and specificity.