The arthritogenic
peptide hypothesis has inspired research aimed at defining the
peptide-presenting properties of
HLA-B27 subtypes and their relation to
ankylosing spondylitis. Various studies have shed new light on the influence of
HLA-B27 polymorphism in modulating
peptide binding and T-cell antigen presentation. Moreover, multiple factors along the antigen processing-loading pathway, including
tapasin, contribute to shaping the
HLA-B27 repertoire. Other studies have revealed significant
peptide-binding similarities between
HLA-B27 and subtypes of
HLA-B39, supporting a role of this
antigen in
spondyloarthropathy. A putative pathogenetic role of the
HLA-B27 heavy chain, initially suggested from studies in transgenic mice, is claimed on the basis of novel, yet circumstantial, evidence concerning an apparently unusual capacity of the heavy chain to form stable homodimers or misfold after biosynthesis. Finally, it appears that arthritogenic
infections might downregulate
HLA-B27 expression, favoring bacterial survival. The specificity and mechanism of this phenomenon are yet to be defined.