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- Title
HLA-B27 lacking associated β2-microglobulin rearranges to auto-display or cross-display residues 169–181: a novel molecular mechanism for spondyloarthropathies
- Authors
Luthra-Guptasarma, Manni; Singh, Balvinder
- Abstract
Expression of the MHC class I allelle, 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 β2m-free, peptide-free heavy chains support a helix-coil transition in the segment leading from the α2 domain to the α3 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.
- Subjects
SPONDYLOARTHROPATHIES; SPINE diseases; ARTHRITIS; AUTOIMMUNE diseases
- Publication
FEBS Letters, 2004, Vol 575, Issue 1-3, p1
- ISSN
0014-5793
- Publication type
Article
- DOI
10.1016/j.febslet.2004.08.037