title: Influence of inflammation-related changes on conformational characteristics of HLA-B27 subtypes as detected by IR spectroscopy.
abstract: Inflammatory processes are accompanied by the post-translational modification of certain arginine residues to yield citrulline, and a pH decrease in the affected tissue, which might influence the protonation of histidine residues within proteins. We employed isotope-edited IR spectroscopy to investigate whether conformational features of two human major histocompatibility antigen class I subtypes, HLA-B*2705 and HLA-B*2709, are affected by these changes. Both differ only in residue 116 (Asp vs. His) within the peptide-binding grooves, but are differentially associated with inflammatory rheumatic disorders. Our analyses of the two HLA-B27 subtypes in complex with a modified self-peptide containing a citrulline RRKWURWHL (U = citrulline) revealed that the heavy chain is more flexible in the HLA-B*2705 subtype than in the HLA-B*2709 subtype. Together with our previous studies of HLA-B27 subtypes complexed with the unmodified self-peptide RRKWRRWHL, these findings support the existence of subtype-specific conformational features of the heavy chains under physiological conditions, which are undetectable by X-ray crystallography and exist irrespective of the sequence of the bound peptide and its binding mode. They might thus influence antigenic properties of the respective HLA-B27 subtype. Furthermore, a decrease in the pH from 7.5 to 5.6 during the analyses had an influence only on HLA-B*2709 complexed with the unmodified self-peptide, where His116 is not contacted by any peptide side chain. This permits us to conclude that histidines, and in particular His116, influence the stability of MHC:peptide complexes. The conditions prevailing in inflammatory environments in vivo might thus also exert an impact on selected conformational features of HLA-B27:peptide complexes.
authors.affiliation: Robert Koch-Institut, Berlin, Germany.
authors.forename: Heinz
authors.initials: H
authors.lastname: Fabian
authors.forename: Bernhard
authors.initials: B
authors.lastname: Loll
authors.forename: Hans
authors.initials: H
authors.lastname: Huser
authors.forename: Dieter
authors.initials: D
authors.lastname: Naumann
authors.forename: Barbara
authors.initials: B
authors.lastname: Uchanska-Ziegler
authors.forename: Andreas
authors.initials: A
authors.lastname: Ziegler
mesh_terms: D015235:HLA-B Antigens / Q000737:chemistry*; D015796:HLA-B27 Antigen / Q000737:chemistry / Q000235:genetics*; D006639:Histidine / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D055550:Protein Stability; D013055:Spectrophotometry, Infrared; D013167:Spondylitis, Ankylosing / Q000235:genetics
chemical_list: D015235:HLA-B Antigens; C464936:HLA-B*27:05 antigen; C464937:HLA-B*27:09 antigen; D015796:HLA-B27 Antigen; D006639:Histidine