Cutting edge: HLA-B27 can form a novel beta 2-microglobulin-free heavy chain homodimer structure.
HLA-B27 has a striking association with inflammatory arthritis. We show that free HLA-B27 heavy chains can form a disulfide-bonded homodimer, dependent on residue Cys67 in their extracellular alpha 1 domain. Despite the absence of beta 2-microglobulin, HLA-B27 heavy chain homodimers (termed HC-B27) were stabilized by a known peptide epitope. HC-B27 complexes were recognized by the conformation-specific Ab W6/32, but not the ME1 Ab. Surface labeling and immunoprecipitation demonstrated the presence of similar W6/32-reactive free heavy chains at the surface of HLA-B27-transfected T2 cells. HC-B27 homodimer formation might explain the ability of HLA-B27 to induce spondyloarthropathy in beta 2-microglobulin-deficient mice.
Allen
R L
RL
Human Immunology Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, United Kingdom.
O'Callaghan
C A
CA
McMichael
A J
AJ
Bowness
P
P
D000918:Antibody Specificity; D000937:Antigen-Antibody Reactions; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D003545:Cysteine / Q000737:chemistry; D019281:Dimerization; D004220:Disulfides / Q000737:chemistry / Q000378:metabolism; D015796:HLA-B27 Antigen / Q000737:chemistry* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D011233:Precipitin Tests; D011487:Protein Conformation; D014162:Transfection / Q000276:immunology; D001613:beta 2-Microglobulin / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism
D004220:Disulfides; D015796:HLA-B27 Antigen; D001613:beta 2-Microglobulin; D003545:Cysteine