HLA-B27-bound peptide repertoires: their nature, origin and pathogenetic relevance

Adv Exp Med Biol. 2009;649:196-209. doi: 10.1007/978-1-4419-0298-6_14.

Abstract

Peptide binding is a central biological property of HLA-B27. The availability of HLA-B27 subtypes differentially associated to ankylosing spondylitis provides a unique tool to explore the relationship between peptide specificity and pathogenetic potential. Many studies have focused on defining the nature of subtype-bound repertoires, aiming to identify peptide features that may correlate with association to disease and to find constitutive self-ligands with sequence homology to microbial epitopes. These studies were pursued on the assumption that molecular mimicry between self and foreign ligands of HLA-B27 might trigger autoimmunity. A second level of involvement ofpeptide repertoires in the biology and immunopathology of HLA-B27 is through their critical influence on folding, maturation and cell surface expression and stability. Recent studies have emphasized the mechanisms ofpeptide loading and optimization, the interactions ofHLA-B27 with other components of the peptide-loading complex and the contribution of these interactions to shaping HLA-B27-bound peptide repertoires. A novel, more comprehensive and integrative, view is emerging in which the peptide binding specificity is a critical determinant of the whole HLA-B27 biology. A proper understanding of the relationships between peptide specificity and other molecular and functional features of HLA-B27 should provide the key to unveiling its pathogenetic role in spondyloarthritis.

Publication types

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

MeSH terms

  • HLA-B27 Antigen* / genetics
  • HLA-B27 Antigen* / metabolism
  • Humans
  • Ligands
  • Peptides* / genetics
  • Peptides* / metabolism
  • Polymorphism, Genetic
  • Proteasome Endopeptidase Complex / metabolism
  • Protein Binding / genetics
  • Protein Binding / immunology
  • Spondylitis, Ankylosing* / genetics
  • Spondylitis, Ankylosing* / immunology

Substances

  • HLA-B27 Antigen
  • Ligands
  • Peptides
  • Proteasome Endopeptidase Complex