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

Journal article

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.

Authors: Colbert, R; Rowland-Jones, S; Mcmichael, A; Frelinger, J

• Journal: Immunity
• Volume: 1
• Issue: 2
• Pages: 121-130
• Publication date: 1994-05-01
• DOI: 10.1016/1074-7613(94)90105-8
• EISSN: 1097-4180
• ISSN: 1074-7613
• Language: English
• Keywords: Peptides; Protein Binding; Antigen Presentation; Influenza A virus; Binding Sites; RNA-Binding Proteins; Nucleoproteins; T-Lymphocytes, Cytotoxic; Humans; Viral Core Proteins; Amino Acid Sequence; Alleles; DNA; Spinal Diseases; Mutagenesis, Site-Directed; Arthritis; Molecular Sequence Data; HLA-B27 Antigen; Base Sequence