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

Michal Almani, Shai Raffaeli, Tal Vider-Shalit, Lea Tsaban, Vered Fishbain, Yoram Louzoun

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


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.

Original languageEnglish
Pages (from-to)1056-1065
Number of pages10
JournalEuropean Journal of Immunology
Issue number4
StatePublished - 2009


  • Autoimmunity
  • Bioinformatics
  • CD8 T cells
  • Self/non-self-discrimination


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