Dual, HLA-B27 subtype-dependent conformation of a self-peptide.

Abstract

The products of the human leukocyte antigen subtypes HLA-B*2705 and HLA-B*2709 differ only in residue 116 (Asp vs. His) within the peptide binding groove but are differentially associated with the autoimmune disease ankylosing spondylitis (AS); HLA-B*2705 occurs in AS-patients, whereas HLA-B*2709 does not. The subtypes also generate differential T cell repertoires as exemplified by distinct T cell responses against the self-peptide pVIPR (RRKWRRWHL). The crystal structures described here show that pVIPR binds in an unprecedented dual conformation only to HLA-B*2705 molecules. In one binding mode, peptide pArg5 forms a salt bridge to Asp116, connected with drastically different interactions between peptide and heavy chain, contrasting with the second, conventional conformation, which is exclusively found in the case of B*2709. These subtype-dependent differences in pVIPR binding link the emergence of dissimilar T cell repertoires in individuals with HLA-B*2705 or HLA-B*2709 to the buried Asp116/His116 polymorphism and provide novel insights into peptide presentation by major histocompatibility antigens.

• Authors: Martin Hülsmeyer, Maria Teresa Fiorillo, Francesca Bettosini, Rosa Sorrentino, Wolfram Saenger, Andreas Ziegler, Barbara Uchanska-Ziegler
• Journal: The Journal of experimental medicine (J Exp Med) Vol. 199 Issue 2 Pg. 271-81 (Jan 19 2004) ISSN: 0022-1007 [Print] United States
• PMID: 14734527 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• HLA-B Antigens
• HLA-B*27:05 antigen
• HLA-B*27:09 antigen
• HLA-B27 Antigen

Topics

• Amino Acid Sequence
• Binding Sites (genetics)
• Cell Line
• HLA-B Antigens (chemistry, genetics, metabolism)
• HLA-B27 Antigen (chemistry, classification, genetics, metabolism)
• Humans
• Models, Molecular
• Protein Binding
• Protein Conformation
• Spondylitis, Ankylosing (genetics, immunology)
• Static Electricity
• T-Lymphocytes, Cytotoxic (immunology)