Dynamics of Ankylosing Spondylitis-associated Arthritogenic Peptide-MHC I interactions

Abstract Ankylosing spondylitis (AS) is a chronic inflammatory disorder affecting the axial skeleton and often associated with Human Leukocyte Antigen-B*27 (HLA-B*27) positivity. HLA-B*27 and its role in AS pathogenesis remain unclear despite the identification of multiple susceptibility alleles. As the most frequent subtype related to AS, HLA-B*27:05 differs from the non-associated HLA-B*27:09 subtype at a single position. This study focuses on the comparison of two subtypes in their binding to two arthritogenic peptides (ARGQPGVMG-DRASFIKNL) and a viral peptide (KK10) through 500 ns long molecular dynamic simulations. In the present study, it was found that peptide-MHC I complex stability and peptide presentation were similar when the peptides had similar C-terminal charges.