Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication

DOI

10.1038/ni835

Type

Journal article

Journal

Nat Immunol

Publication Date

10/2002

Volume

3

Pages

940 - 943

Keywords

Animals, B-Lymphocytes, Cell Line, Cross Reactions, Crystallography, X-Ray, HLA-DR Antigens, HLA-DRB1 Chains, HLA-DRB5 Chains, Herpesvirus 4, Human, Humans, Mice, Mice, Transgenic, Models, Molecular, Multiple Sclerosis, Myelin Basic Protein, Protein Structure, Tertiary, Receptors, Antigen, T-Cell, alpha-beta