The immunodominant myeloperoxidase T-cell epitope induces local cell-mediated injury in antimyeloperoxidase glomerulonephritis.
Microscopic polyangiitis is an autoimmune small-vessel vasculitis that often manifests as focal and necrotizing glomerulonephritis and renal failure. Antineutrophil cytoplasmic Abs (ANCAs) specific for myeloperoxidase (MPO) play a role in this disease, but the role of autoreactive MPO-specific CD4(+...
Huvudupphovsmän: | , , , , , , |
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Materialtyp: | Journal article |
Språk: | English |
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2012
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author | Ooi, J Chang, J Hickey, M Borza, D Fugger, L Holdsworth, SR Kitching, A |
author_facet | Ooi, J Chang, J Hickey, M Borza, D Fugger, L Holdsworth, SR Kitching, A |
author_sort | Ooi, J |
collection | OXFORD |
description | Microscopic polyangiitis is an autoimmune small-vessel vasculitis that often manifests as focal and necrotizing glomerulonephritis and renal failure. Antineutrophil cytoplasmic Abs (ANCAs) specific for myeloperoxidase (MPO) play a role in this disease, but the role of autoreactive MPO-specific CD4(+) T cells is uncertain. By screening overlapping peptides of 20 amino acids spanning the MPO molecule, we identified an immunodominant MPO CD4(+) T-cell epitope (MPO(409-428)). Immunizing C57BL/6 mice with MPO(409-428) induced focal necrotizing glomerulonephritis similar to that seen after whole MPO immunization, when MPO was deposited in glomeruli. Transfer of an MPO(409-428)-specific CD4(+) T-cell clone to Rag1(-/-) mice induced focal necrotizing glomerulonephritis when glomerular MPO deposition was induced either by passive transfer of MPO-ANCA and LPS or by planting MPO(409-428) conjugated to a murine antiglomerular basement membrane mAb. MPO(409-428) also induced biologically active anti-MPO Abs in mice. The MPO(409-428) epitope has a minimum immunogenic core region of 11 amino acids, MPO(415-426), with several critical residues. ANCA-activated neutrophils not only induce injury but lodged the autoantigen MPO in glomeruli, allowing autoreactive anti-MPO CD4(+) cells to induce delayed type hypersensitivity-like necrotizing glomerular lesions. These studies identify an immunodominant MPO T-cell epitope and redefine how effector responses can induce injury in MPO-ANCA-associated microscopic polyangiitis. |
first_indexed | 2024-03-07T04:33:56Z |
format | Journal article |
id | oxford-uuid:cf49bb8f-35e5-47e8-aa46-e9a21a81d3dd |
institution | University of Oxford |
language | English |
last_indexed | 2024-03-07T04:33:56Z |
publishDate | 2012 |
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spelling | oxford-uuid:cf49bb8f-35e5-47e8-aa46-e9a21a81d3dd2022-03-27T07:41:24ZThe immunodominant myeloperoxidase T-cell epitope induces local cell-mediated injury in antimyeloperoxidase glomerulonephritis.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:cf49bb8f-35e5-47e8-aa46-e9a21a81d3ddEnglishSymplectic Elements at Oxford2012Ooi, JChang, JHickey, MBorza, DFugger, LHoldsworth, SRKitching, AMicroscopic polyangiitis is an autoimmune small-vessel vasculitis that often manifests as focal and necrotizing glomerulonephritis and renal failure. Antineutrophil cytoplasmic Abs (ANCAs) specific for myeloperoxidase (MPO) play a role in this disease, but the role of autoreactive MPO-specific CD4(+) T cells is uncertain. By screening overlapping peptides of 20 amino acids spanning the MPO molecule, we identified an immunodominant MPO CD4(+) T-cell epitope (MPO(409-428)). Immunizing C57BL/6 mice with MPO(409-428) induced focal necrotizing glomerulonephritis similar to that seen after whole MPO immunization, when MPO was deposited in glomeruli. Transfer of an MPO(409-428)-specific CD4(+) T-cell clone to Rag1(-/-) mice induced focal necrotizing glomerulonephritis when glomerular MPO deposition was induced either by passive transfer of MPO-ANCA and LPS or by planting MPO(409-428) conjugated to a murine antiglomerular basement membrane mAb. MPO(409-428) also induced biologically active anti-MPO Abs in mice. The MPO(409-428) epitope has a minimum immunogenic core region of 11 amino acids, MPO(415-426), with several critical residues. ANCA-activated neutrophils not only induce injury but lodged the autoantigen MPO in glomeruli, allowing autoreactive anti-MPO CD4(+) cells to induce delayed type hypersensitivity-like necrotizing glomerular lesions. These studies identify an immunodominant MPO T-cell epitope and redefine how effector responses can induce injury in MPO-ANCA-associated microscopic polyangiitis. |
spellingShingle | Ooi, J Chang, J Hickey, M Borza, D Fugger, L Holdsworth, SR Kitching, A The immunodominant myeloperoxidase T-cell epitope induces local cell-mediated injury in antimyeloperoxidase glomerulonephritis. |
title | The immunodominant myeloperoxidase T-cell epitope induces local cell-mediated injury in antimyeloperoxidase glomerulonephritis. |
title_full | The immunodominant myeloperoxidase T-cell epitope induces local cell-mediated injury in antimyeloperoxidase glomerulonephritis. |
title_fullStr | The immunodominant myeloperoxidase T-cell epitope induces local cell-mediated injury in antimyeloperoxidase glomerulonephritis. |
title_full_unstemmed | The immunodominant myeloperoxidase T-cell epitope induces local cell-mediated injury in antimyeloperoxidase glomerulonephritis. |
title_short | The immunodominant myeloperoxidase T-cell epitope induces local cell-mediated injury in antimyeloperoxidase glomerulonephritis. |
title_sort | immunodominant myeloperoxidase t cell epitope induces local cell mediated injury in antimyeloperoxidase glomerulonephritis |
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