Peptide/MHC Detachment

The binding between a peptide and a major histocompatibility complex (MHC) is one of the most important processes for the induction of an adaptive immune response. Many algorithms have been developed to predict peptide/MHC (pMHC) binding. However, no approach has yet been able to give structural insight into how peptides detach from the MHC. In the study, (Bioinformatics 32(2):181-186 (2016)) we used a combination of coarse graining, hierarchical natural move Monte Carlo and stochastic conformational optimization to explore this process. The first step in the project was the definition of natural structural segment (regions), which are used in the definition of natural moves. The structral regions for an MHC/Peptide complex is illustrated below.

Peptide/MHC complex

Structure of the peptide/MHC (pMHC) complex HLA-A*02:01 based on PDB accession code 3PWN. The peptide is bound above the beta-sheet floor and flanked by two kinked alpha-helices. The decomposition of the pMHC complex into regions as used in this study is illustrated with (transparent) surfaces. Blue: MHC beta-floor; red: peptide; orange/yellow: whole MHC helices broken by kinks. For clarity, the a3 region and the b2-microglobulin are not shown.