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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.

Original publication

DOI

10.1016/1074-7613(94)90105-8

Type

Journal article

Journal

Immunity

Publication Date

05/1994

Volume

1

Pages

121 - 130

Addresses

Department of Microbiology and Immunology, University of North Carolina, Chapel Hill 27599-7290.

Keywords

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