CD8+ T-cell mediated self-reactivity in HLA-B27 context as a consequence of dual peptide conformation

Clin Immunol. 2010 Jun;135(3):476-82. doi: 10.1016/j.clim.2010.01.009. Epub 2010 Feb 18.

Abstract

HLA-B2709 does not predispose for Ankylosing Spondylitis although it differs from B2705, the most common and AS-associated subtype in different ethnic groups, only for the substitution His116Asp. Therefore, a productive approach to elucidate the molecular mechanisms of the disease could be the comparison of these alleles. B2705 has been shown to display certain self-peptides enriched in basic residues i.e., pVIPR and pGR, in a dual conformation and this is accompanied by the presence of specific cytotoxic T cells in patients with AS. In this study, we convalidate our previous observation that B2709 healthy subjects do not possess primary reactivity towards pVIPR while showing a prompt CD8+ T cell response driven by pGR. Notably, in the B2709 context of presentation, pVIPR assumes only a single conformation in contrast with pGR which is dimorphic. These results suggest a possible general connection between the occurrence of double peptide conformation and the property of inducing specific autoimmune responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen Presentation / immunology
  • Autoantigens / chemistry
  • Autoantigens / immunology
  • Autoimmunity / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cross Reactions / immunology
  • HLA-B Antigens / immunology*
  • HLA-B27 Antigen / immunology*
  • Humans
  • Lymphocyte Activation / immunology
  • Peptides / chemistry
  • Peptides / immunology
  • Protein Conformation
  • Spondylitis, Ankylosing / immunology*

Substances

  • Autoantigens
  • HLA-B Antigens
  • HLA-B*27:05 antigen
  • HLA-B*27:09 antigen
  • HLA-B27 Antigen
  • Peptides