1uxw: Difference between revisions

==Overview==

Molecular mimicry is discussed as a possible mechanism that may contribute, to the development of autoimmune diseases. It could also be involved in, the differential association of the human major histocompatibility, subtypes HLA-B(*)2705 and HLA-B(*)2709 with ankylosing spondylitis. These, two subtypes differ only in residue 116 of the heavy chain (Asp in, B(*)2705 and His in B(*)2709), but the reason for the differential disease, association is not understood. Using x-ray crystallography, we show here, that the viral peptide pLMP2 (RRRWRRLTV, derived from latent membrane, protein 2 (residues 236-244) of Epstein-Barr virus) is presented by the, B(*)2705 and B(*)2709 molecules in two drastically deviating, conformations. Extensive structural similarity between pLMP2 and the, self-peptide pVIPR (RRKWRRWHL, derived from vasoactive intestinal peptide, type 1 receptor (residues 400-408)) is observed only when the peptides are, presented by B(*)2705 because of a salt bridge between Arg(5) of both, peptides and the subtype-specific heavy chain residue Asp(116). Combined, with functional studies using pLMP2/pVIPR-cross-reactive cytotoxic T cell, lines and clones, together with target cells presenting these peptides or, a modified peptide analogue, our results reveal that a pathogen-derived, peptide can exhibit major histocompatibility complex class I, subtype-dependent, drastically distinct binding modes. Furthermore, the, results demonstrate that molecular mimicry between pLMP2 and pVIPR in the, HLA-B27 context is an allele-dependent property.

==About this Structure==

[[Category: mhc (major histocompatibility complex)]]