Human self‐protein CD8+ T‐cell epitopes are both positively and negatively selected

The cellular immune system recognizes self‐epitopes in the context of MHC‐I molecules. The immunological general view presumes that these self‐epitopes are just a background, both positively and negatively selecting T cells. We here estimate the number of epitopes in each human protein for many frequent HLA alleles, and a score representing over or under presentation of epitopes on these proteins. We further show that there is a clear selection for the presentation of specific self‐protein types. Proteins presenting many epitopes include, for example, autoimmune regulator (AIRE) upregulated tissue‐specific antigens, immune system receptors and proteins with a high expression level. On the other hand, proteins that may be considered less “useful” for the immune system, such as low expression level proteins, are under‐presented. We combine our epitope estimate with single nucleotide polymorphism (SNP) measures to show that this selection can be directly observed through the fraction of non‐synonymous SNP (replacement fraction), which is significantly higher inside epitopes than outside.