Differential association of HLA-B*2705 and B*2709 to ankylosing spondylitis correlates with limited peptide subsets but not with altered cell surface stability.

Abstract

In contrast to HLA-B*2705, B*2709 is weakly or not associated to ankylosing spondylitis. Both allotypes differ by a single D116H change. We compared the B*2705- and B*2709-bound peptide repertoires by mass spectrometry to quantify the effect of B*2709 polymorphism on peptide specificity. In addition, shared and differentially bound ligands were sequenced to define the structural features of the various peptide subsets. B*2705 shared 79% of its peptide repertoire with B*2709. Shared ligands accounted for 88% of the B*2709-bound repertoire. All B*2705 ligands not bound to B*2709 had C-terminal basic or Tyr residues. Most B*2709-bound peptides had C-terminal aliphatic and Phe residues, but two showed C-terminal Arg or Tyr. The B*2709-bound repertoire included 12% of peptides not found in B*2705. These had aliphatic C-terminal residues, which are also favored in B*2705. However, these peptides bound weakly B*2705 in vitro, indicating distinct contribution of secondary anchor residues in both subtypes. Differences in peptide binding did not affect the ratio of native to beta2-microglobulin-free HLA-B27 heavy chain at the cell surface. Our results suggest that weaker association of B*2709 with ankylosing spondylitis is based on differential binding of a limited subset of natural ligands by this allotype.

• Authors: Manuel Ramos, Alberto Paradela, Miriam Vazquez, Anabel Marina, Jesus Vazquez, Jose A Lopez de Castro
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 277 Issue 32 Pg. 28749-56 (Aug 09 2002) ISSN: 0021-9258 [Print] United States
• PMID: 12042320 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Epitopes
• HLA-B Antigens
• HLA-B*27:05 antigen
• HLA-B*27:09 antigen
• HLA-B27 Antigen
• Ligands
• Peptides
• Tyrosine
• DNA
• Arginine

Topics

• Amino Acid Sequence
• Antibodies, Monoclonal (metabolism)
• Arginine (chemistry)
• Cell Line
• Cell Membrane (metabolism)
• DNA (metabolism)
• Dose-Response Relationship, Drug
• Epitopes
• Flow Cytometry
• HLA-B Antigens (chemistry)
• HLA-B27 Antigen (chemistry, metabolism)
• Humans
• Ligands
• Mass Spectrometry
• Molecular Sequence Data
• Mutagenesis, Site-Directed
• Peptides (chemistry, metabolism)
• Protein Binding
• Protein Structure, Tertiary
• Spondylitis, Ankylosing (immunology, metabolism)
• Transfection
• Tyrosine (chemistry)