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The ADAMTS13 1239–1253 peptide is a dominant HLA-DR1-restricted CD4 + T-cell epitope

Abstract : Acquired thrombotic thrombocytopenic purpura is a rare and severe disease characterized by auto-antibodies directed against “A Disintegrin And Metalloproteinase with Thrombospondin type 1 repeats, 13th member" (ADAMTS13), a plasma protein involved in hemostasis. Involvement of CD4+ T cells in the pathogenesis of the disease is suggested by the IgG isotype of the antibodies. However, the nature of the CD4+ T-cell epitopes remains poorly characterized. Here, we determined the HLA-DR-restricted CD4+ T-cell epitopes of ADAMTS13. Candidate T-cell epitopes were predicted in silico and binding affinities were confirmed in competitive enzyme-linked immunosorbent assays. ADAMTS13-reactive CD4+ T-cell hybridomas were generated following immunization of HLA-DR1 transgenic mice (Sure-L1 strain) and used to screen the candidate epitopes. We identified the ADAMTS131239–1253 peptide as the single immunodominant HLA-DR1-restricted CD4+ T-cell epitope. This peptide is located in the CUB2 domain of ADAMTS13. It was processed by dendritic cells, stimulated CD4+ T cells from Sure-L1 mice and was recognized by CD4+ T cells from an HLA-DR1-positive patient with acute thrombotic thrombocytopenic purpura. Interestingly, the ADAMTS131239–1253 peptide demonstrated promiscuity towards HLA-DR11 and HLA-DR15. Our work paves the way towards the characterization of the ADAMTS13-specific CD4+ T-cell response in patients with thrombotic thrombocytopenic purpura using ADAMTS131239–1253-loaded HLA-DR tetramers.
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https://hal-normandie-univ.archives-ouvertes.fr/hal-02379896
Contributor : Jean-Baptiste Latouche <>
Submitted on : Monday, November 25, 2019 - 10:33:22 PM
Last modification on : Tuesday, October 13, 2020 - 3:46:08 PM

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Laurent Gilardin, Sandrine Delignat, Ivan Peyron, Mathieu Ing, Yu-Chun Lone, et al.. The ADAMTS13 1239–1253 peptide is a dominant HLA-DR1-restricted CD4 + T-cell epitope. Haematologica, Ferrata Storti Foundation, 2017, 102 (11), pp.1833-1841. ⟨10.3324/haematol.2015.136671⟩. ⟨hal-02379896⟩

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