Differences in peptide presentation between B27 subtypes: the importance of the P1 side chain in maintaining high affinity peptide binding to B*2703

Immunity. 1994 May;1(2):121-30. doi: 10.1016/1074-7613(94)90105-8.


Susceptibility to spondyloarthropathies is strongly associated with the MHC class I molecule HLA-B27, and is hypothesized to result from the presentation of arthritogenic peptides. Subtypes of B27 that differ structurally but are disease-associated ought to be capable of presenting such peptides, while nondisease-associated subtypes would not. We demonstrate that B*2703, the predominant West African B27 subtype that may not predispose to disease, is not recognized by most B*2705-alloreactive CTL, and does not efficiently present a known B*2705-restricted influenza A nucleoprotein (NP) peptide. We show inefficient presentation is due to a reduced binding affinity of B*2703 for the NP peptide. Furthermore, substituting Arg for the naturally occurring Ser at P1 of the NP peptide, restores high affinity binding and efficient presentation by B*2703. Our results suggest that B*2703 will bind and present efficiently only a subset of the peptides that bind to B*2705, in particular those with Arg or Lys at P1. The apparent lack of disease in individuals with B*2703 may be due to an inability to bind and present putative arthritogenic peptides.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Antigen Presentation*
  • Arthritis / genetics
  • Arthritis / immunology
  • Base Sequence
  • Binding Sites / genetics
  • DNA / genetics
  • HLA-B27 Antigen / classification
  • HLA-B27 Antigen / genetics
  • HLA-B27 Antigen / metabolism*
  • Humans
  • Influenza A virus / genetics
  • Influenza A virus / immunology
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Nucleocapsid Proteins
  • Nucleoproteins / genetics
  • Nucleoproteins / immunology
  • Peptides / genetics
  • Peptides / immunology*
  • Peptides / metabolism
  • Protein Binding
  • RNA-Binding Proteins*
  • Spinal Diseases / genetics
  • Spinal Diseases / immunology
  • T-Lymphocytes, Cytotoxic / immunology
  • Viral Core Proteins / genetics
  • Viral Core Proteins / immunology


  • HLA-B27 Antigen
  • NP protein, Influenza A virus
  • Nucleocapsid Proteins
  • Nucleoproteins
  • Peptides
  • RNA-Binding Proteins
  • Viral Core Proteins
  • DNA