Detailed motifs for peptide binding to HLA-A*0201 derived from large random sets of peptides using a cellular binding assay.
Extensive sets of in total about 2000 synthetic peptides were investigated for their binding affinities to HLA-A*0201. Comparisons of the amino acid compositions of binding to nonbinding sets of peptides provided new information concerning the rules for 9-, 10-, and 11-mer peptide binding at the amino acid level. Preferred primary anchors were shown to depend on peptide length, longer peptides being more demanding in this respect. A clear preference exists for certain amino acids at several nonanchor positions. In addition, the presence of particular amino acids at those positions almost completely precludes peptide binding. We found no evidence for preferred anchor pairs. From these results new and detailed HLA-A*0201 peptide-binding motifs for 9-, 10-, and 11-mer peptide binding were deduced. The motifs are in accordance with earlier reports but include new findings, including C as a C-terminal anchor, the importance of D at positions 4 for binding, and the deleterious effect of R at position 5 (in 9-mers). The motifs are presented in such a way that they can be used to predict peptide binding to HLA-A*0201 by computer analysis (see accompanying paper [56]).
Drijfhout
J W
JW
Department of Immunohematology and Blood Bank, University Hospital Leiden, The Netherlands.
Brandt
R M
RM
D'Amaro
J
J
Kast
W M
WM
Melief
C J
CJ
D000483:Alleles; D000595:Amino Acid Sequence; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000737:chemistry; D000954:Antigens, Surface / Q000737:chemistry; D015815:Cell Adhesion Molecules / Q000737:chemistry; D002460:Cell Line; D000071858:Epithelial Cell Adhesion Molecule; D015234:HLA-A Antigens / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D027383:Papillomaviridae / Q000378:metabolism; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology*; D011485:Protein Binding / Q000276:immunology*
D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule; D015234:HLA-A Antigens; D010455:Peptides