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

Abstract

Most patients with rheumatoid arthritis express particular HLA–DR alleles. The DRβI 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. Inlymphoblastoid 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–DRβ1 chain in these two rheumatoid arthritis–associated alleles.

Cite this article

Auger, I., Escola, J., Gorvel, J. et al. HLA–DR4 and HLA–DR10 motifs that carry susceptibility to rheumatoid arthritis bind 70–kD heat shock proteins. Nat Med 2, 306–310 (1996). https://doi.org/10.1038/nm0396-306

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