Cell (26 October 2017) doi:10.1016/j.cell.2017.09.050

The major histocompatibility class I (MHCI) genotype determines the sub-peptidome that can be effectively presented. In Cell, Carter and colleagues show that a ‘presentation score’ derived from MHCI’s binding affinities to residues of interest can identify mutations with a high likelihood of generating neoantigens, and they use this score to evaluate individual MHCI genotypes as a determinant of the antigenicity of cancer mutations. In 9,176 patients with known HLA alleles, the score identified individual variation in the presentation of 1,018 mutations in known oncogenes and tumor suppressors. The analysis indicates that patients have a higher probability of acquiring mutations less effectively presented by their MHCI, which indicates that the frequency of a mutation is not determined only by fitness advantage. The MHCI genotype provides predictive information about the mutations likely to occur in a particular person should a tumor arise, but the score cannot predict which patients are at higher risk for a mutation of known probability and is more predictive in some tumor types than others.IV