HLA‐B27 lacking associated β2‐microglobulin rearranges to auto‐display or cross‐display residues 169–181: a novel molecular mechanism for spondyloarthropathies

Expression of the MHC class I allele, HLA-B27, is correlated with autoimmune disease. The misfolding and association of B27 heavy chains through non-native disulfide bonds has recently been implicated. Here, we propose that beta2m-free, peptide-free heavy chains support a helix-coil transition in the segment leading from the alpha2 domain to the alpha3 domain, facilitating rotation of backbone angles around residues 167/168, and allowing residues 169-181 (identical to a known B27 ligand) to loop around and occupy the molecule's own peptide-binding cleft. Such 'auto-display', occurring either within B27 molecules, or between B27 molecules, could provoke autoimmune attack.