title: Identification of an HLA-DQ2 peptide binding motif and HLA-DPw3-bound self-peptide by pool sequencing.
abstract: Molecules of the major histocompatibility complex (MHC) present antigenic peptides to T cells. Sequencing peptide pools eluted from MHC class I molecules has established allele-specific peptide binding motifs. We applied pool sequencing to analyze human MHC class II-bound peptides and found that HLA-DQ2-eluted peptides predominantly contained lysine, isoleucine, and phenylalanine at relative position i, i + 3 and i + 8, respectively. These residues putatively represent anchor residues for MHC binding. Analysis of a heterogeneous HLA-DPw3/DPw4-eluted peptide pool yielded a sequence matching an epitope from the endogenous enzyme glyceraldehyde-3-phosphate dehydrogenase. This self-peptide and a partially identical, known allo-epitope bound specifically to DPw3 and DR13 molecules, suggesting the sharing of a binding motif. In particular, the presence of an arginine at relative position 4 appeared important for binding to these HLA class II specificities. Thus, pool sequencing is applicable for the analysis of MHC class II-eluted peptides.
authors.affiliation: Department of Immunohematology and Bloodbank, University Hospital, Leiden, The Netherlands.
authors.forename: F A
authors.initials: FA
authors.lastname: Verreck
authors.forename: A
authors.initials: A
authors.lastname: van de Poel
authors.forename: A
authors.initials: A
authors.lastname: Termijtelen
authors.forename: R
authors.initials: R
authors.lastname: Amons
authors.forename: J W
authors.initials: JW
authors.lastname: Drijfhout
authors.forename: F
authors.initials: F
authors.lastname: Koning
mesh_terms: D000595:Amino Acid Sequence; D001324:Autoantigens / Q000737:chemistry; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000737:chemistry / Q000276:immunology; D006682:HLA-DP Antigens / Q000378:metabolism*; D006683:HLA-DQ Antigens / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D013329:Structure-Activity Relationship
chemical_list: D001324:Autoantigens; D006682:HLA-DP Antigens; D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; D010455:Peptides; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases