HLA-DR4 and HLA-DR10 motifs that carry susceptibility to rheumatoid arthritis bind 70-kD heat shock proteins

Nat Med. 1996 Mar;2(3):306-10. doi: 10.1038/nm0396-306.


Most patients with rheumatoid arthritis express particular HLA-DR alleles. The DRbeta1 chains of these alleles share a highly homologous amino acid motif, in their third hypervariable (HV3) region, and this motif seems to help the development of rheumatoid arthritis via unknown mechanisms. In an attempt to identify a ligand of this motif, we screened bacterial proteins. HV3 peptides from HLA-DRB1 alleles containing a QKRAA or RRRAA motif bound the 70-kD heat shock protein (HSP) from Escherichia coli, dnaK. In lymphoblastoid cells homozygous for these same HLA-DRB1 alleles the constitutive 70-kD HSP, HSP73, that targets selected proteins to lysosomes coprecipitated with HLA-DR. Thus the QKRAA and RRRAA amino acid motifs of HLA-DR mediate binding of HLA-DR to HSP73. This property may influence the intracellular route, processing or peptide associations of the HLA-DRbeta1 chain in these two rheumatoid arthritis-associated alleles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Arthritis, Rheumatoid / etiology
  • Arthritis, Rheumatoid / genetics*
  • Arthritis, Rheumatoid / immunology*
  • Bacterial Proteins / metabolism
  • Carrier Proteins / metabolism
  • Escherichia coli / metabolism
  • Escherichia coli Proteins*
  • HLA-DR4 Antigen / genetics*
  • HLA-DR4 Antigen / metabolism*
  • HSC70 Heat-Shock Proteins
  • HSP70 Heat-Shock Proteins / metabolism*
  • Humans
  • In Vitro Techniques
  • Kinetics
  • Ligands
  • Molecular Sequence Data
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism
  • Protein Binding


  • Bacterial Proteins
  • Carrier Proteins
  • Escherichia coli Proteins
  • HLA-DR4 Antigen
  • HSC70 Heat-Shock Proteins
  • HSP70 Heat-Shock Proteins
  • HSPA8 protein, human
  • Ligands
  • Peptide Fragments
  • dnaK protein, E coli