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.
Almani
Michal
M
Math Department, Bar Ilan University, Ramat Gan, Israel.
Raffaeli
Shai
S
Vider-Shalit
Tal
T
Tsaban
Lea
L
Fishbain
Vered
V
Louzoun
Yoram
Y
D000483:Alleles; D001324:Autoantigens / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019295:Computational Biology; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D005787:Gene Frequency / Q000235:genetics / Q000276:immunology; D015894:Genome, Human / Q000235:genetics / Q000276:immunology; D006649:Histocompatibility Antigens / Q000235:genetics / Q000276:immunology*; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics / Q000276:immunology
D001324:Autoantigens; D018984:Epitopes, T-Lymphocyte; D006649:Histocompatibility Antigens