X-ray crystal structure of HLA-DR4 (DRA*0101, DRB1*0401) complexed with a peptide from human collagen II

Immunity. 1997 Oct;7(4):473-81. doi: 10.1016/s1074-7613(00)80369-6.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Animals
  • Arthritis, Rheumatoid / immunology
  • Binding Sites
  • Collagen / chemistry
  • Collagen / immunology*
  • Collagen / ultrastructure
  • Crystallography, X-Ray
  • Dimerization
  • Enterotoxins / chemistry
  • Epitope Mapping
  • HLA-DR4 Antigen / genetics
  • HLA-DR4 Antigen / ultrastructure*
  • Humans
  • Mice
  • Mice, Transgenic
  • Models, Molecular
  • Peptides / chemistry
  • Peptides / immunology
  • Protein Conformation
  • Protein Structure, Tertiary
  • Recombinant Proteins
  • Superantigens / chemistry


  • Enterotoxins
  • HLA-DR4 Antigen
  • Peptides
  • Recombinant Proteins
  • Superantigens
  • enterotoxin B, staphylococcal
  • Collagen

Associated data