Dipeptides catalyze rapid peptide exchange on MHC class I molecules

Significance We have shown previously that dipeptides can support efficient in vitro folding of the MHC class I molecules. Here, we describe the discovery of dipeptides that catalyze the dissociation of low- and high-affinity peptides from class I and their replacement for exogenous peptides of interest, on both recombinant and cell surface HLA-A*02:01, HLA-B*27:05, and H-2K b molecules. Understanding peptide exchange on class I will help us understand peptide optimization in live cells. We demonstrate that the peptide-exchange technology can be used to produce epitope-specific MHC tetramers much faster and more easily than possible with techniques currently available and to enhance peptide loading onto live cells for cancer immunotherapy. Further applications include allotype specific peptide epitope elution from tumor cells.