HLA-B27-bound peptide repertoires: their nature, origin and pathogenetic relevance.
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.
de Castro
Jose A López
JA
Centro de Biología molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid Cantoblanco, Madrid, Spain. aldecastro@cbm.uam.es
D015796:HLA-B27 Antigen / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008024:Ligands; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D011110:Polymorphism, Genetic; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D013167:Spondylitis, Ankylosing / Q000235:genetics / Q000276:immunology
D015796:HLA-B27 Antigen; D008024:Ligands; D010455:Peptides; D046988:Proteasome Endopeptidase Complex