The normal functioning of the immune system requires several molecular interactions to take place. These could be the presentation of foreign antigens that are required in the defense against pathogens, or the maturation of immune cells. Equally important is to understand when the immune system goes wrong, for example in autoimmune diseases such as multiple sclerosis and rheumatoid arthritis.
The selection of immunogenic peptides by MHC class I molecules in the endoplasmic reticulum has major implications for immune system stimulation and may present an intervention point to treat disease. A weakly-interacting multi-protein peptide loading complex mediates this selection process via modulation of MHC class I conformation; peptide optimisation critically depends on an intermediate state. We are investigating the structural dynamics of the MHC-peptide complex using nuclear magnetic resonance, a technique that is uniquely placed to detect the structural plasticity that cannot be observed in X-ray crystal structures.
High-quality spectra of 2H13C15N-labelled MHC class I have enabled backbone assignment of both the H-2Db α-chain and the hβ2M subunit, whilst relaxation data and residual dipolar couplings have permitted examination of the backbone dynamics.
PDRA: Dr Halina Mikolajek
PhD: Mary Beton
Supervisor: Dr Joern Werner
PhD research: Modelling antigen processing by ERAP1 and MHC Class I
Funding: BBSRC, Microsoft
Primary research group: Molecular and Cellular Biosciences