Definition of the peptide binding motif within DRB1*1401 restricted epitopes by peptide competition and structural modeling.
This study identified the peptide-binding motif of HLA-DRA/DRB1*1401 (DR1401). First, peptides containing DR1401 restricted epitopes were identified using tetramer-guided epitope mapping. Among these, an influenza B peptide was selected for the motif study. After confirming the binding register for this peptide using a set of arginine substitutions, binding affinities were determined for 33 peptides derived from this influenza B sequence with single amino acid substitutions. The DR1401 peptide-binding motif was deduced from the relative binding affinities of these peptides and confirmed by structural modeling. Pocket 1 demonstrated a preference for aliphatic anchor residues and methionine. Pocket 4 accommodated methionine and aliphatic residues, but also allowed some polar and charged amino acids. Pocket 6 preferred basic residues but also allowed some polar and aliphatic amino acids. Pocket 9 preferred aliphatic and aromatic amino acids and tolerated some polar residues but excluded all charged residues. Together these preferences define a distinct set of peptides that can be presented by DR1401. The resulting motif was used to verify T cell epitopes within the novel antigenic peptides identified by tetramer-guided epitope mapping and within peptides from published reports that contain putative DR1401 epitopes.
James
Eddie A
EA
Benaroya Research Institute at Virginia Mason, Seattle, WA 98101, USA.
Moustakas
Antonis K
AK
Berger
Deanna
D
Huston
Laurie
L
Papadopoulos
George K
GK
Kwok
William W
WW
D020816:Amino Acid Motifs; D019943:Amino Acid Substitution; D001665:Binding Sites; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D006684:HLA-DR Antigens / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D059811:HLA-DRB1 Chains; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D006801:Humans; D009981:Influenza B virus / Q000276:immunology; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D018984:Epitopes, T-Lymphocyte; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D010455:Peptides; D011994:Recombinant Proteins