Studying MHC-I genotype restriction on the set of expressed mutations across different cancer types

MHC-I molecules expose the intracellular protein content on the cell surface, allowing T cells to detect foreign or mutated peptides. The combination of six MHC-I alleles each individual carries defines the sub-peptidome that can be effectively presented. Interestingly, it was previously found that the MHC-I genotype restricts the landscape of oncogenic mutations (Marty et al., 2017). In addition, in a previous work we found that only ~30% of the mutations accumulated in the DNA are sufficiently expressed (Yizhak et al. 2019). Subsequently, in this study we examine the hypothesis that mutations that arise in the DNA but are not transcribed to the RNA are under positive selection dictated by the specific MHC-I genotype of different individuals. To validate this hypothesis, we examine the binding potential of transcribed and non-transcribed somatic mutations to the corresponding individual`s MHC-I genotype. We then perform a genome-wide comparison of their presentation score both at the individual level and across samples and cancer types. In the meeting we will present first results of this analysis in several cancer types, as well as the association of patients’ presentation score with survival rate and immune cell infiltrate.