Modulation of peptide binding by HLA-B27 polymorphism in pockets A and B, and peptide specificity of B*2703

Eur J Immunol. 1995 Aug;25(8):2370-7. doi: 10.1002/eji.1830250837.


The results in this study address three aspects of peptide binding to the disease-associated antigen HLA-B27 and its modulation by polymorphism: the contribution of major anchor residues 2 and 9, the role of pocket B polymorphism in modulating peptide specificity, and the binding properties of B*2703, a subtype not found to be associated with spondyloarthropathy. Synthetic analogs of peptides naturally presented by B*2705 were used to demonstrate that residue 2 is essential, since Ala2 analogs bound marginally to B*2705, but the specificity of B*2705 for Arg2 is not absolute, and show that the contribution of basic residue 9 to binding was significant, but less than Arg2. The effect of single mutations in the B pocket was to decrease or--with the Glu > Met-45 mutation--totally shift pocket B specificity for Arg2 towards other residues at this position. This was shown by quantitating the relative binding of Gln2 and Ala2 analogs, and by pool-sequencing of the peptides bound in vivo to these mutants. Peptides naturally presented by B*2705 apparently bound with a lower affinity to pocket A variants with altered hydrogen bonding to the peptide N terminus, including B*2703. Binding of peptide analogs with changes at positions 2 or 9 suggested that in B*2703 pocket A, interactions are weaker and pocket B interactions are stronger than in B*2705. This can be explained by the effect of the unique His59 change in B*2703 in both pockets. Thus, B*2703 is probably the HLA-B27 sub-type with the most stringent specificity for the Arg2 peptide motif.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cell Line
  • Drug Stability
  • HLA-B27 Antigen / genetics
  • HLA-B27 Antigen / immunology*
  • HLA-B27 Antigen / metabolism*
  • Humans
  • Molecular Sequence Data
  • Mutation / genetics
  • Peptide Biosynthesis
  • Protein Binding / genetics
  • Transfection


  • HLA-B27 Antigen