X-Ray Crystal Structure of HLA-DR4 (DRA0101, DRB10401) Complexed with a Peptide from Human Collagen II

Dessen A, Lawurence CM, Cupo S +2 more1997ImmunityOther

10.1016/s1074-7613(00)80369-6 PubMed Free full text

Immune/Innate

Abstract

Genetic predisposition to rheumatoid arthritis (RA) is linked to the MHC class II allele HLA-DR4. The charge of the amino acid at DRbeta71 in the peptide-binding site appears to be critical in discriminating DR molecules linked to increased disease susceptibility. We have determined the 2.5 A x-ray structure of the DR4 molecule with the strongest linkage to RA (DRB1*0401) complexed with a human collagen II peptide. Details of a predicted salt bridge between lysine DRbeta71 and aspartic acid at the P4 peptide position suggest how it may participate in both antigen binding and TCR activation. A model is proposed for the DR4 recognition of collagen II (261-273), an antigen immunodominant in human-transgenic mouse models of RA.

Key Biomarkers

HLA-DR4 (DRA*0101, DRB1*0401)HLA-DR4 DRbeta71 lysine residue

Symptom Clusters

Rheumatoid Arthritis (RA)

Cited By (1)

Genetic factors affecting the occurrence, clinical phenotype, and outcome of autoimmune hepatitisClinical Gastroenterology and Hepatology · 2008

X-Ray Crystal Structure of HLA-DR4 (DRA*0101, DRB1*0401) Complexed with a Peptide from Human Collagen II

X-Ray Crystal Structure of HLA-DR4 (DRA0101, DRB10401) Complexed with a Peptide from Human Collagen II