Antigen presentation

Inside every cell, proteins are continuously degraded and a sample of the resulting peptides is loaded onto MHC/HLA molecules and shipped to the surface. This antigen-presentation pathway is how the immune system audits what each cell is doing.

A tumor mutation only matters for a vaccine if its peptide survives this pathway and gets presented. Many promising-looking neoantigens fail because they're never actually presented — which is why prediction models increasingly try to model the whole processing pathway, not just final binding.