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Identification des épitopes T d’ADAMTS13 chez les patients atteints de Purpura Thrombotique Thrombocytopénique

Abstract : Thrombotic thrombocytopenic purpura (TTP) is a rare and severe disease characterized by auto-antibodies directed against ADAMTS13 (A13), a plasmatic protein involved in haemostasis. The implication of CD4⁺ T cells in the pathogenesis of the disease is suggested by the existence of a restriction to particular HLA-DR alleles and by the IgG isotype of the antibodies. In this study, we wished to determine the T cell epitopes of A13. First, we selected in silico the immunodominant peptides, based on their binding capacity to HLA-DR11 molecules. Second, their binding capacity to purified HLA-DR11 molecules using a ELISA competitive assay led us to identify the best binder peptides. Finally, we determined the peptides recognized by human CD4⁺ T cells from DR11 healthy donors and patients. These results were reproduced for the HLA-DR1 haplotype and in a transgenic humanized HLA-DR1 mouse model. In a perspective point of view, our results will allow us to further isolate the specific CD4⁺ T cells in order to characterize them at different steps of the disease and during follow-up to better anticipate relapses.
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Submitted on : Tuesday, May 19, 2020 - 5:14:08 PM
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Laurent Gilardin. Identification des épitopes T d’ADAMTS13 chez les patients atteints de Purpura Thrombotique Thrombocytopénique. Immunité adaptative. Université Paris-Saclay, 2019. Français. ⟨NNT : 2019SACLS520⟩. ⟨tel-02612959⟩

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