Interaction between HSP73 and HLA-DRB1*0401: implications for the development of rheumatoid arthritis.
The amino acid motif QKRAA on HLA-DRB1*0401 carries susceptibility to develop rheumatoid arthritis through unknown mechanisms. We identified the original functions of this motif. In B-cells, HSP73, the constitutive 70-kDa heat-shock protein (HSP), associates with HLA-DRB1*0401. This interaction causes abnormal trafficking of HLA-DRB1*0401. Indeed, HSP73 targets HLA-DRB1*0401 from endoplasmic reticulum to lysosomes bypassing the normal route through the Golgi apparatus and endosomes. In this article, we propose mechanisms to explain how 70-kDa HSPs might contribute to rheumatoid arthritis.
Auger
Isabelle
I
INSERM U639, Immuno-rhumatologie, Faculté de Médecine, 27 boulevard Jean Moulin, 13005 Marseille, France.
Roudier
Jean
J
D020816:Amino Acid Motifs; D017951:Antigen Presentation / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000502:physiology; D011992:Endosomes / Q000502:physiology; D006056:Golgi Apparatus / Q000502:physiology; D006684:HLA-DR Antigens / Q000276:immunology* / Q000378:metabolism; D059811:HLA-DRB1 Chains; D050883:HSC70 Heat-Shock Proteins / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008247:Lysosomes / Q000502:physiology; D011485:Protein Binding; D021381:Protein Transport
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553505:HLA-DRB1*04:01 antigen; D050883:HSC70 Heat-Shock Proteins; C494371:HSPA8 protein, human