Endogenous peptides bound to HLA-A3 possess a specific combination of anchor residues that permit identification of potential antigenic peptides.
A motif specific to peptides that bind to the human class I major histocompatibility complex molecule HLA-A3 was identified by sequence analysis of HPLC fractions containing endogenous peptides. Twenty-six different sequences were obtained, 19 of which were nonamers. The majority of these endogenous peptide sequences contained Leu at position (P)2, while most sequences contained Tyr or Lys at P9. In addition, Phe was shared by 16 sequences at P3. Synthetic peptides corresponding to endogenous peptide sequences were shown to bind to HLA-A3. The importance of Leu at P2 and Tyr or Lys at P9 ("anchor" residues) for peptide binding to HLA-A3 was demonstrated by the following results: (i) peptides GLFGGGGGY, GLFGGGGGK, and GLGGGGFGY, but not GLFGGGGGV, specifically bound to HLA-A3 and (ii) six nonapeptides from within the influenza A nucleoprotein, matrix, and polymerase proteins, selected for synthesis based upon their possession of P2 and P9 anchor residues, were shown to bind HLA-A3. In contrast, none of a set of eight peptides that bound to HLA-A2, or six that bound to HLA-B27, bound detectably to HLA-A3. These findings provide a rationale for the design and selection of peptides that can be recognized by HLA-A3-restricted T cells.
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
Knierman
M
M
Lukszo
J
J
Turner
R V
RV
Biddison
W E
WE
Coligan
J E
JE
D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D002461:Cell Line, Transformed; D002846:Chromatography, Affinity; D002851:Chromatography, High Pressure Liquid; D000939:Epitopes / Q000032:analysis; D015789:HLA-A2 Antigen / Q000235:genetics / Q000378:metabolism; D015791:HLA-A3 Antigen / Q000235:genetics / Q000378:metabolism*; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D010455:Peptides / Q000302:isolation & purification / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D013329:Structure-Activity Relationship; D014162:Transfection
D000939:Epitopes; D015789:HLA-A2 Antigen; D015791:HLA-A3 Antigen; D009838:Oligodeoxyribonucleotides; D010446:Peptide Fragments; D010455:Peptides