1. Transmembrane Helices Are an Over-Presented and Evolutionarily Conserved Source of Major Histocompatibility Complex Class I and II Epitopes.
- Author
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Bilderbeek RJC, Baranov MV, van den Bogaart G, and Bianchi F
- Subjects
- Alleles, Antigen Presentation immunology, Chromosomes genetics, Chromosomes immunology, Cytoplasm genetics, Cytoplasm immunology, Epitopes, T-Lymphocyte immunology, Histocompatibility Antigens Class I immunology, Histocompatibility Antigens Class II immunology, Humans, Membrane Proteins immunology, Peptides genetics, Peptides immunology, Polymorphism, Single Nucleotide genetics, Polymorphism, Single Nucleotide immunology, T-Lymphocytes, Helper-Inducer immunology, Antigen Presentation genetics, Epitopes, T-Lymphocyte genetics, Histocompatibility Antigens Class I genetics, Histocompatibility Antigens Class II genetics, Membrane Proteins genetics, Protein Structure, Secondary genetics
- Abstract
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 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 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bilderbeek, Baranov, van den Bogaart and Bianchi.)
- Published
- 2022
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