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Induction of HLA-B27 heavy chain homodimer formation after activation in dendritic cells
Arthritis Research & Therapy, 09/05/08

Santos SG et al. – HLA-B27 heavy chain dimer formation can be induced upon dendritic cell activation, implying that these novel structures may not be displayed to the immune system at all times. Thus the behaviour of HLA-B27 on dendritic cells may be important in the study of inflammatory arthritis.

Methods

Aim was to study the formation of HLA-B27 heavy chain homodimers in dendritic cells
Cell lines studied: dendritic like cell lines and monocyte derived dendritic cells from peripheral blood
The KG-1 dendritic-like cell line was transfected with HLA-B27 cDNA constructs
Cellular distribution, intracellular assembly and ability of HLA-B27 to form heavy chain homodimers vs human monocyte-derived dendritic cells after stimulation with LPS was studied

Results

Cells expressing HLA-B27 display an intracellular source of MHC class I heavy chain partially overlapping with the Golgi, but not the endoplasmic reticulum, was lost upon cell maturation with PMA and ionomycin
Formation of HLA-B27 homodimers was induced upon maturation, with a transient induction also seen in LPS stimulated human monocyte-derived dendritic cells expressing HLA-B27
The weak association of wildtype HLA-B*2705 with the transporter associated with antigen processing (TAP) could also be enhanced by mutation of residues at position 114 and 116 in the peptide-binding groove to those present in the HLA-B*2706 allele

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