Journal Article

Opening opportunities for K d determination and screening of MHC peptide complexes

Günther, Christian, Niebling, Stephan, Garcia-Alai, Maria, Anjanappa, Raghavendra, Springer, Sebastian, Uetrecht, Charlotte, Saikia, Ankur, Kopicki, Janine-Denise

2022

Overview

An essential element of adaptive immunity is selective binding of peptide antigens by major histocompatibility complex (MHC) class I proteins and their presentation to cytotoxic T lymphocytes. Using native mass spectrometry, we analyze the binding of peptides to an empty disulfide-stabilized HLA-A*02:01 molecule and, due to its unique stability, we determine binding affinities of complexes loaded with truncated or charge-reduced peptides. We find that the two anchor positions can be stabilized independently, and we further analyze the contribution of additional amino acid positions to the binding strength. As a complement to computational prediction tools, our method estimates binding strength of even low-affinity peptides to MHC class I complexes quickly and efficiently. It has huge potential to eliminate binding affinity biases and thus accelerate drug discovery in infectious diseases, autoimmunity, vaccine design, and cancer immunotherapy.

• Publisher: Nature Portfolio