Endogenous peptides with distinct amino acid anchor residue motifs bind to HLA-A1 and HLA-B8.
Distinct amino acid (aa) residue motifs for peptides binding to HLA-A1 and HLA-B8 were identified by sequence analyses of reversed-phase HPLC fractions containing endogenous peptides derived from these HLA molecules. Fifteen different primary sequences were determined for HLA-A1-associated peptides, 12 of which were nine aa in length. Common features among these peptide sequences were Tyr at the COOH-terminus, a negatively charged aa (usually Glu) at position 3 (P3), and Pro at P4. Twenty-seven different primary sequence assignments were made for HLA-B8-associated peptides, most of which were eight aa in length. Lys, and in a few cases Arg, predominated at P3 and P5; Leu and Pro predominated at P2, and Leu was the preferred COOH-terminal residue. Unlike all other human class I molecules whose peptide-binding properties have been studied, both HLA-A1 and HLA-B8 endogenous peptide sequences have a dominant anchor residue at P3, and these aa are opposite in charge to the aa at position 156 of the peptide-binding site. Synthetic peptides corresponding to endogenous peptide sequences bound to their respective HLA molecules in vitro, indicating that they derive from peptides bound to HLA and not from copurifying contaminants. Eight of the HLA-A1 and HLA-B8 endogenous peptide sequences matched intracellularly expressed proteins found in protein sequence data bases. The HLA-A1 peptide-binding motif was then used to identify potential antigenic peptides from influenza A viral proteins that bound to HLA-A1 in vitro.
DiBrino
M
M
Biological Resources Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
Parker
K C
KC
Shiloach
J
J
Turner
R V
RV
Tsuchida
T
T
Garfield
M
M
Biddison
W E
WE
Coligan
J E
JE
D000595:Amino Acid Sequence; D000956:Antigens, Viral / Q000276:immunology; D001483:Base Sequence; D017931:DNA Primers / Q000737:chemistry; D000939:Epitopes; D015788:HLA-A1 Antigen / Q000378:metabolism*; D015795:HLA-B8 Antigen / Q000378:metabolism*; D006801:Humans; D009980:Influenza A virus / Q000276:immunology; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding; D013329:Structure-Activity Relationship
D000956:Antigens, Viral; D017931:DNA Primers; D000939:Epitopes; D015788:HLA-A1 Antigen; D015795:HLA-B8 Antigen; D010455:Peptides