Relevance of residue 116 of HLA‐B27 in determining susceptibility to ankylosing spondylitis

Mauro D'amato, Maria Teresa Fiorillo, Carlo Carcassi, Alessandro Mathieu, Angelo Zuccarelli, Pier Paolo Bitti, Roberto Tosi, Rosa Sorrentino

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Abstract

Ankylosing spondylitis (AS) is an autoimmune disorder strongly associated with HLA‐B27. A direct role of B27 molecules in the disease pathogenesis has been postulated, possibly by presenting to T cells an as‐yet unidentified arthritogenic peptide that triggers the autoimmune response. There are nine HLA‐B27 alleles differing from each other at one or more amino acid positions. It is important, for the identification of the arthritogenic peptide, to define which alleles, and therefore which polymorphic positions, predispose to the disease. Here, we report that HLA‐B2709 is not associated with AS, as it was not found in patients. HLA‐B2709 differs from the most frequent and disease‐associated HLA‐B2705 allele for a single substitution (His vs. Asp) at position 116. Amino acid 116 is located at the bottom of the groove where the antigenic peptide sits, and it has been proven to influence the peptide‐binding specificity of HLA class I molecules. The most likely interpretation of these data is that the differences in charge and size that accompany the His‐to‐Asp substitution exclude the acceptance of the arthritogenic peptide.

Original languageEnglish
Pages (from-to)3199-3201
Number of pages3
JournalEuropean Journal of Immunology
Volume25
Issue number11
DOIs
Publication statusPublished - 1 Jan 1995
Externally publishedYes

Keywords

  • Ankylosing spondylitis
  • Arthritogenic peptide
  • HLA‐B27

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