Auger I, Escola J M, Gorvel J P, Roudier J
Laboratoire d'Immuno-Rhumatologie, Faculté de Médecine de Marseille, France.
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.
大多数类风湿性关节炎患者表达特定的HLA - DR等位基因。这些等位基因的DRβ1链在其第三个高变区（HV3）共享一个高度同源的氨基酸基序，并且该基序似乎通过未知机制促进类风湿性关节炎的发展。为了鉴定该基序的配体，我们筛选了细菌蛋白。来自含有QKRAA或RRRAA基序的HLA - DRB1等位基因的HV3肽与来自大肠杆菌的70-kD热休克蛋白（HSP）dnaK结合。在这些相同HLA - DRB1等位基因纯合的淋巴母细胞中，将选定蛋白质靶向溶酶体的组成型70-kD HSP即HSP73与HLA - DR共沉淀。因此，HLA - DR的QKRAA和RRRAA氨基酸基序介导HLA - DR与HSP73的结合。这一特性可能会影响这两个与类风湿性关节炎相关的等位基因中HLA - DRβ1链的细胞内途径、加工或肽缔合。
