AUTHOR=Bianchi Frans , Textor Johannes , van den Bogaart Geert 

TITLE=Transmembrane Helices Are an Overlooked Source of Major Histocompatibility Complex Class I Epitopes

JOURNAL=Frontiers in Immunology

VOLUME=Volume 8 - 2017

YEAR=2017

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2017.01118

DOI=10.3389/fimmu.2017.01118

ISSN=1664-3224

ABSTRACT=About a fourth of the human proteome is anchored by transmembrane helices to lipid membranes. Transmembrane helices require multiple hydrophobic residues for spanning membranes, and this shows a striking resemblance with the requirements for peptide binding to major histocompatibility complex (MHC) class I. It therefore comes as no surprise that bio-informatics analysis predicts an over-representation of transmembrane helices among strong MHC class I binders. Published peptide elution studies confirm that transmembrane helices are indeed presented by MHC class I. This raises the question how membrane proteins are processed for MHC class I (cross-)presentation, with current research focusing on soluble antigens. The presentation of membrane-buried peptides is likely important in health and disease, as transmembrane helices are considerably conserved and their presentation might prevent escape mutations by pathogens. Therefore, it could contribute to the disease correlations described for many HLA haplotypes.