The biochemistry and immunology of non-canonical forms of HLA-B27
HLA-B27 (B27) is strongly associated with the spondyloarthritides. B27 is expressed at the cell surface of antigen presenting cells (APC) both as canonical β2m-associated and non-canonical β2m-free heavy chain (FHC) forms which include B27 dimers (termed B272). B27 FHC forms arise in an endosomal co...
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| Format: | Journal article |
| Language: | English |
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2014
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| _version_ | 1797059036015755264 |
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| author | Shaw, J Hatano, H Kollnberger, S |
| author_facet | Shaw, J Hatano, H Kollnberger, S |
| author_sort | Shaw, J |
| collection | OXFORD |
| description | HLA-B27 (B27) is strongly associated with the spondyloarthritides. B27 is expressed at the cell surface of antigen presenting cells (APC) both as canonical β2m-associated and non-canonical β2m-free heavy chain (FHC) forms which include B27 dimers (termed B272). B27 FHC forms arise in an endosomal compartment from recycling β2m-associated B27. Formation of cell surface FHC dimers is critically dependent on an unpaired reactive cysteine 67 in the α1 helix of the class I heavy chain. HLA-B27 also form redox-inducible β2m-associated dimers on exosomes and apoptosing cells. By contrast with cell surface expressed cysteine 67-dependent heavy chain dimers these dimers are dependent on a cytoplasmic cysteine 325 for their formation.HLA-B27 binds to immunoregulatory receptors including members of the Killer cell Immunoglobulin-like (KIR) and Leukocyte Immunoglobulin-like receptor family. B27 FHC bind to different but overlapping sets of these immunoreceptors compared to classical β2m-associated HLA-B27. B27 FHC bind more strongly to KIR3DL2 and LILRB2 immune receptor than other β2m-associated HLA-class I ligands. Genetic studies have implicated genes which control production of the important proinflammatory cytokine IL-17 in the pathogenesis of spondyloarthritis. Cell surface HLA-B27 FHC binding to these immune receptors or acting through other mechanisms could impact on the pathogenesis of spondyloarthritis by promoting immune cell production of IL-17. Here we review the literature on these non-canonical forms of HLA-B27 and the immune receptors they bind to and discuss the possible relevance of these interactions to the pathogenesis of spondyloarthropathy. © 2013 Elsevier Ltd. |
| first_indexed | 2024-03-06T19:58:33Z |
| format | Journal article |
| id | oxford-uuid:267a6540-441c-425d-8ed7-7ce12c7240a3 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:58:33Z |
| publishDate | 2014 |
| record_format | dspace |
| spelling | oxford-uuid:267a6540-441c-425d-8ed7-7ce12c7240a32022-03-26T12:01:14ZThe biochemistry and immunology of non-canonical forms of HLA-B27Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:267a6540-441c-425d-8ed7-7ce12c7240a3EnglishSymplectic Elements at Oxford2014Shaw, JHatano, HKollnberger, SHLA-B27 (B27) is strongly associated with the spondyloarthritides. B27 is expressed at the cell surface of antigen presenting cells (APC) both as canonical β2m-associated and non-canonical β2m-free heavy chain (FHC) forms which include B27 dimers (termed B272). B27 FHC forms arise in an endosomal compartment from recycling β2m-associated B27. Formation of cell surface FHC dimers is critically dependent on an unpaired reactive cysteine 67 in the α1 helix of the class I heavy chain. HLA-B27 also form redox-inducible β2m-associated dimers on exosomes and apoptosing cells. By contrast with cell surface expressed cysteine 67-dependent heavy chain dimers these dimers are dependent on a cytoplasmic cysteine 325 for their formation.HLA-B27 binds to immunoregulatory receptors including members of the Killer cell Immunoglobulin-like (KIR) and Leukocyte Immunoglobulin-like receptor family. B27 FHC bind to different but overlapping sets of these immunoreceptors compared to classical β2m-associated HLA-B27. B27 FHC bind more strongly to KIR3DL2 and LILRB2 immune receptor than other β2m-associated HLA-class I ligands. Genetic studies have implicated genes which control production of the important proinflammatory cytokine IL-17 in the pathogenesis of spondyloarthritis. Cell surface HLA-B27 FHC binding to these immune receptors or acting through other mechanisms could impact on the pathogenesis of spondyloarthritis by promoting immune cell production of IL-17. Here we review the literature on these non-canonical forms of HLA-B27 and the immune receptors they bind to and discuss the possible relevance of these interactions to the pathogenesis of spondyloarthropathy. © 2013 Elsevier Ltd. |
| spellingShingle | Shaw, J Hatano, H Kollnberger, S The biochemistry and immunology of non-canonical forms of HLA-B27 |
| title | The biochemistry and immunology of non-canonical forms of HLA-B27 |
| title_full | The biochemistry and immunology of non-canonical forms of HLA-B27 |
| title_fullStr | The biochemistry and immunology of non-canonical forms of HLA-B27 |
| title_full_unstemmed | The biochemistry and immunology of non-canonical forms of HLA-B27 |
| title_short | The biochemistry and immunology of non-canonical forms of HLA-B27 |
| title_sort | biochemistry and immunology of non canonical forms of hla b27 |
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