title: HLA class I allele promiscuity revisited.
abstract: The peptide repertoire presented on human leukocyte antigen (HLA) class I molecules is largely determined by the structure of the peptide binding groove. It is expected that the molecules having similar grooves (i.e., belonging to the same supertype) might present similar/overlapping peptides. However, the extent of promiscuity among HLA class I ligands remains controversial: while in many studies T cell responses are detected against epitopes presented by alternative molecules across HLA class I supertypes and loci, peptide elution studies report minute overlaps between the peptide repertoires of even related HLA molecules. To get more insight into the promiscuous peptide binding by HLA molecules, we analyzed the HLA peptide binding data from the large epitope repository, Immune Epitope Database (IEDB), and further performed in silico analysis to estimate the promiscuity at the population level. Both analyses suggest that an unexpectedly large fraction of HLA ligands (> 50%) bind two or more HLA molecules, often across supertype or even loci. These results suggest that different HLA class I molecules can nevertheless present largely overlapping peptide sets, and that "functional" HLA polymorphism on individual and population level is probably much lower than previously anticipated.
authors.affiliation: Theoretical Biology and Bioinformatics, Utrecht University, Padualaan 8, 3584CH Utrecht, The Netherlands.
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Rao
authors.forename: Ilka
authors.initials: I
authors.lastname: Hoof
authors.forename: Ana Isabel C A Fontaine
authors.initials: AI
authors.lastname: Costa
authors.forename: Debbie
authors.initials: D
authors.lastname: van Baarle
authors.forename: Can
authors.initials: C
authors.lastname: Keşmir
mesh_terms: D000483:Alleles; D017951:Antigen Presentation / Q000276:immunology*; D030562:Databases, Protein; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D006680:HLA Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D006801:Humans; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D011485:Protein Binding / Q000276:immunology
chemical_list: D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens; D010455:Peptides