1H15

X-ray crystal structure of HLA-DRA1*0101/DRB5*0101 complexed with a peptide from Epstein Barr Virus DNA polymerase

Summary for 1H15

• Entry DOI: 10.2210/pdb1h15/pdb
• Related: 1A6A 1AQD 1D5M 1D5X 1D5Z 1D6E 1DLH 1FV1 1HQR 1HXY 1J8H 1KG0 1SEB 2SEB
• Descriptor: HLA CLASS II HISTOCOMPATIBILITY ANTIGEN, DR ALPHA CHAIN, HLA CLASS II HISTOCOMPATIBILITY ANTIGEN, DR BETA 1 CHAIN, DNA POLYMERASE, ... (6 entities in total)
• Functional Keywords: immune system/transferase, complex (mhc-antigen), immune system, mhc, hla, class ii, dr2, drb5, ebv, dna polymerase, dna-directed dna polymerase, immune system-transferase complex
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Cell membrane; Single-pass type I membrane protein: P01903; Host nucleus: P03198
• Total number of polymer chains: 6
• Total formula weight: 91120.68

Authors

Lang, H.,Jacobsen, H.,Ikemizu, S.,Andersson, C.,Harlos, K.,Madsen, L.,Hjorth, P.,Sondergaard, L.,Svejgaard, A.,Wucherpfennig, K.,Stuart, D.I.,Bell, J.I.,Jones, E.Y.,Fugger, L. (deposition date: 2002-07-02, release date: 2002-10-03, Last modification date: 2024-10-23)

Primary citation

Lang, H.,Jacobsen, H.,Ikemizu, S.,Andersson, C.,Harlos, K.,Madsen, L.,Hjorth, P.,Sondergaard, L.,Svejgaard, A.,Wucherpfennig, K.,Stuart, D.I.,Bell, J.I.,Jones, E.Y.,Fugger, L.
A Functional and Structural Basis for Tcr Cross-Reactivity in Multiple Sclerosis
Nat.Immunol., 3:940-, 2002

PubMed Abstract: The multiple sclerosis (MS)-associated HLA major histocompatibility complex (MHC) class II alleles DRB1*1501, DRB5*0101 and DQB1*0602 are in strong linkage disequilibrium, making it difficult to determine which is the principal MS risk gene. Here we show that together the DRB1 and DRB5 loci may influence susceptibility to MS. We demonstrate that a T cell receptor (TCR) from an MS patient recognized both a DRB1*1501-restricted myelin basic protein (MBP) and DRB5*0101-restricted Epstein-Barr virus (EBV) peptide. Crystal structure determination of the DRB5*0101-EBV peptide complex revealed a marked degree of structural equivalence to the DRB1*1501-MBP peptide complex at the surface presented for TCR recognition. This provides structural evidence for molecular mimicry involving HLA molecules. The structural details suggest an explanation for the preponderance of MHC class II associations in HLA-associated diseases.

PubMed: 12244309
DOI: 10.1038/NI835

Experimental method

X-RAY DIFFRACTION (3.1 Å)