Two distinct HLA-A*0101-specific submotifs illustrate alternative peptide binding modes

Akihiro Kondo, John Sidney, Scott Southwood, Marie France Del Guercio, Ettore Appella, Hiroshi Sakamoto, Howard M. Grey, Esteban Celis, Robert W. Chesnut, Ralph T. Kubo, Alessandro Sette

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Previous studies have defined two different peptide binding motifs specific for HLA-A*0101. These motifs are characterized by the presence of tyrosine (Y) at the C-termini of 9-mer and 10-mer peptides, and either a small polar or hydrophobic (S, T, M) residue in position 2, or a negatively charged (D or E) residue in position 3. In this study, the structural requirements for peptide binding to A*0101 have been further analyzed by examining the binding capacity of large sets of peptides corresponding to naturally occurring sequences which bore one or the other of these two A*0101-specific motifs. By correlating the presence of specific residue types at each position along the peptide sequence with increased (or decreased) binding affinity, the prominent influence of secondary anchor residues was revealed. In most cases, the two anchors in positions 2 and 3 appear to act synergistically. With the exception of the DE3 submotif in 9-mer peptides, a positive role for aromatic residues in position 1 and the center of the peptide (positions 4 or 5 of 9- or 10-mer peptides, respectively), and proline at C-3, were also consistently detected. However, secondary anchor residues also appear to differ significantly between the two different submotifs, demonstrating that A*0101 can utilize alternative modes in binding its peptide ligands. According to these analyses, specific refined submotifs were also established, and their merit verified by independent sets of potential A*0101 binding peptides. Besides providing useful insight into the nature of the interaction of the A*0101 allele with its peptide ligands, such refined motifs should also facilitate accurate prediction of potential A*0101-restricted peptide epitopes.

Original languageEnglish (US)
Pages (from-to)249-258
Number of pages10
JournalImmunogenetics
Volume45
Issue number4
DOIs
StatePublished - Jan 1 1997
Externally publishedYes

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HLA-A Antigens
Peptides
Ligands
Proline
Tyrosine
Epitopes
Alleles

ASJC Scopus subject areas

  • Immunology
  • Genetics

Cite this

Kondo, A., Sidney, J., Southwood, S., Del Guercio, M. F., Appella, E., Sakamoto, H., ... Sette, A. (1997). Two distinct HLA-A*0101-specific submotifs illustrate alternative peptide binding modes. Immunogenetics, 45(4), 249-258. https://doi.org/10.1007/s002510050200

Two distinct HLA-A*0101-specific submotifs illustrate alternative peptide binding modes. / Kondo, Akihiro; Sidney, John; Southwood, Scott; Del Guercio, Marie France; Appella, Ettore; Sakamoto, Hiroshi; Grey, Howard M.; Celis, Esteban; Chesnut, Robert W.; Kubo, Ralph T.; Sette, Alessandro.

In: Immunogenetics, Vol. 45, No. 4, 01.01.1997, p. 249-258.

Research output: Contribution to journalArticle

Kondo, A, Sidney, J, Southwood, S, Del Guercio, MF, Appella, E, Sakamoto, H, Grey, HM, Celis, E, Chesnut, RW, Kubo, RT & Sette, A 1997, 'Two distinct HLA-A*0101-specific submotifs illustrate alternative peptide binding modes', Immunogenetics, vol. 45, no. 4, pp. 249-258. https://doi.org/10.1007/s002510050200
Kondo A, Sidney J, Southwood S, Del Guercio MF, Appella E, Sakamoto H et al. Two distinct HLA-A*0101-specific submotifs illustrate alternative peptide binding modes. Immunogenetics. 1997 Jan 1;45(4):249-258. https://doi.org/10.1007/s002510050200
Kondo, Akihiro ; Sidney, John ; Southwood, Scott ; Del Guercio, Marie France ; Appella, Ettore ; Sakamoto, Hiroshi ; Grey, Howard M. ; Celis, Esteban ; Chesnut, Robert W. ; Kubo, Ralph T. ; Sette, Alessandro. / Two distinct HLA-A*0101-specific submotifs illustrate alternative peptide binding modes. In: Immunogenetics. 1997 ; Vol. 45, No. 4. pp. 249-258.
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