Transmembrane Helices Are an Over-Presented and Evolutionarily Conserved Source of Major Histocompatibility Complex Class I and II Epitopes

Transmembrane Helices Are an Over-Presented and Evolutionarily Conserved Source of Major Histocompatibility Complex Class I and II Epitopes

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Cytolytic T cell responses are predicted to be biased towards membrane proteins.The peptide-binding grooves of most alleles of histocompatibility complex class I (MHC-I) are relatively hydrophobic, therefore peptide fragments derived from human transmembrane helices (TMHs) are predicted to be presented more often neflintw-r6mpw as would be expected based on their abundance in the proteome.However, the physiological reason of why membrane proteins might be over-presented is unclear.In this study, we show that the predicted over-presentation of TMH-derived peptides is general, as it is predicted for bacteria and viruses cga 200 to cga 510 adapter and for both MHC-I and MHC-II, and confirmed by re-analysis of epitope databases.

Moreover, we show that TMHs are evolutionarily more conserved, because single nucleotide polymorphisms (SNPs) are present relatively less frequently in TMH-coding chromosomal regions compared to regions coding for extracellular and cytoplasmic protein regions.Thus, our findings suggest that both cytolytic and helper T cells are more tuned to respond to membrane proteins, because these are evolutionary more conserved.We speculate that TMHs are less prone to mutations that enable pathogens to evade T cell responses.