The C-terminal extension landscape of naturally presented HLA-I ligands
Guillaume P., Picaud S., Baumgaertner P., Montandon N., Schmidt J., Speiser DE., Coukos G., Bassani-Sternberg M., Filippakopoulos P., Gfeller D.
Significance HLA-I molecules play a central role in immune recognition of infected or cancer cells. They bind short intracellular peptides of 9 to 12 amino acids and present them to T cells for immune recognition. For many years, the confinement of HLA-I ligand has been a central dogma in immunology. Combing analysis of mass spectrometry data with novel algorithms, X-ray crystallography, and T cell recognition assays, we show that a substantial fraction of HLA-I molecules bind peptides extending beyond the C terminus of canonical ligands, and that these peptides can be recognized by CD8 T cells. Our ability to accurately predict such epitopes will help studying their role in infectious diseases or cancer immunotherapy.