title: MHC class I dimer formation by alteration of the cellular redox environment and induction of apoptosis.
abstract: Many MHC class I molecules contain unpaired cysteine residues in their cytoplasmic tail domains, the function of which remains relatively uncharacterized. Recently, it has been shown that in the small secretory vesicles known as exosomes, fully folded MHC class I dimers can form through a disulphide bond between the cytoplasmic tail domain cysteines, induced by the low levels of glutathione in these extracellular vesicles. Here we address whether similar MHC class I dimers form in whole cells by alteration of the redox environment. Treatment of the HLA-B27-expressing Epstein-Barr virus-transformed B-cell line Jesthom, and the leukaemic T-cell line CEM transfected with HLA-B27 with the strong oxidant diamide, and the apoptosis-inducing and glutathione-depleting agents hydrogen peroxide and thimerosal, induced MHC class I dimers. Furthermore, induction of apoptosis by cross-linking FasR/CD95 on CEM cells with monoclonal antibody CH-11 also induced MHC class I dimers. As with exosomal MHC class I dimers, the formation of these structures on cells is controlled by the cysteine at position 325 in the cytoplasmic tail domain of HLA-B27. Therefore, the redox environment of cells intimately controls induction of MHC class I dimers, the formation of which may provide novel structures for recognition by the immune system.
authors: School of Medicine, University of St Andrews, Fife, UK.
authors: Dinara
authors: D
authors: Makhadiyeva
authors: Lorraine
authors: L
authors: Lam
authors: Mohammad
authors: M
authors: Moatari
authors: Jasmine
authors: J
authors: Vallance
authors: Ying
authors: Y
authors: Zheng
authors: Elaine C
authors: EC
authors: Campbell
authors: Simon J
authors: SJ
authors: Powis
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D002460:Cell Line; D019281:Dimerization; D015395:Histocompatibility Antigens Class I / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D010084:Oxidation-Reduction; D013849:Thimerosal / Q000494:pharmacology; D019014:fas Receptor / Q000276:immunology
chemical_list: D015395:Histocompatibility Antigens Class I; D019014:fas Receptor; D013849:Thimerosal; D006861:Hydrogen Peroxide