Induction of HLA-B27 heavy chain homodimer formation after activation in dendritic cells

Santos, Susana G.; Lynch, Sarah; Campbell, Elaine C.; Antoniou, Antony N.; Powis, Simon J.

doi:10.1186/ar2492

Cited by 29 publications

(35 citation statements)

References 29 publications

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“…Under certain physiological conditions, such as enhanced HLA-B27 production following maturation of DCs or in response to cytokines which upregulate MHC class I expression (21,25), HLA-B27 exhibits an enhanced tendency to misfold and aggregate. Such dimerization may result from alterations in the oxidizing environment of the ER, which can accompany the maturation of dendritic cells in response to inflammatory stimuli.…”

Section: Discussionmentioning

confidence: 99%

The MHC Class I Heavy Chain Structurally Conserved Cysteines 101 and 164 Participate in HLA-B27 Dimer Formation

Lenart

Guiliano

Burn

et al. 2012

Antioxidants & Redox Signaling

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Section: Discussionmentioning

confidence: 99%

The MHC Class I Heavy Chain Structurally Conserved Cysteines 101 and 164 Participate in HLA-B27 Dimer Formation

Lenart

Guiliano

Burn

et al. 2012

Antioxidants & Redox Signaling

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“…Consequently, LILRmediated recognition of FHC could represent a novel mechanism of immune regulation by detection of altered conformation of HLA class I complexes. Increased cell surface expression of FHC is associated with the activation of lymphocytes (41)(42)(43)(44)(45)(46)(47) and potentially APCs (73). HLA-C is particularly prone to forming FHC due to its unusual stability in the absence of b 2 m (54,(74)(75)(76)(77), and this form of HLA-C is specifically upregulated during macrophage differentiation (78).…”

Section: Discussionmentioning

confidence: 99%

HLA Class I Allelic Sequence and Conformation Regulate Leukocyte Ig-Like Receptor Binding

Jones

Kosmoliaptsis

Apps

et al. 2011

The Journal of Immunology

110

143

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Leukocyte Ig-like receptors (LILRs) are a family of innate immune receptors predominantly expressed by myeloid cells that can alter the Ag presentation properties of macrophages and dendritic cells. Several LILRs bind HLA class I. Altered LILR recognition due to HLA allelic variation could be a contributing factor in disease. We comprehensively assessed LILR binding to >90 HLA class I alleles. The inhibitory receptors LILRB1 and LILRB2 varied in their level of binding to different HLA alleles, correlating in some cases with specific amino acid motifs. LILRB2 displayed the weakest binding to HLA-B*2705, an allele genetically associated with several autoimmune conditions and delayed progression of HIV infection. We also assessed the effect of HLA class I conformation on LILR binding. LILRB1 exclusively bound folded β2-microglobulin–associated class I, whereas LILRB2 bound both folded and free H chain forms. In contrast, the activating receptor LILRA1 and the soluble LILRA3 protein displayed a preference for binding to HLA-C free H chain. To our knowledge, this is the first study to identify the ligand of LILRA3. These findings support the hypothesis that LILR-mediated detection of unfolded versus folded MHC modulates immune responses during infection or inflammation.

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“…Similarly, we have previously noted that HLA-B27 dimers tend to form in dendritic cells only after activation and significant up-regulation of MHC class I expression. 24 Therefore, MHC class I expression levels and the redox status of cells may both contribute to dimer formation.…”

Section: Discussionmentioning

confidence: 99%

MHC class I dimer formation by alteration of the cellular redox environment and induction of apoptosis

et al. 2012

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SummaryMany 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.

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Induction of HLA-B27 heavy chain homodimer formation after activation in dendritic cells

Cited by 29 publications

References 29 publications

The MHC Class I Heavy Chain Structurally Conserved Cysteines 101 and 164 Participate in HLA-B27 Dimer Formation

The MHC Class I Heavy Chain Structurally Conserved Cysteines 101 and 164 Participate in HLA-B27 Dimer Formation

HLA Class I Allelic Sequence and Conformation Regulate Leukocyte Ig-Like Receptor Binding

MHC class I dimer formation by alteration of the cellular redox environment and induction of apoptosis

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