The ADAMTS131239-1253 peptide is a dominant HLA-DR1-restricted CD4+ T-cell epitope

Haematologica. 2017 Nov;102(11):1833-1841. doi: 10.3324/haematol.2015.136671. Epub 2017 Jul 27.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAMTS13 Protein / chemistry
  • ADAMTS13 Protein / immunology*
  • Alleles
  • Amino Acid Sequence
  • Animals
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / metabolism
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Epitopes, T-Lymphocyte / chemistry
  • Epitopes, T-Lymphocyte / immunology*
  • HLA-DR1 Antigen / chemistry
  • HLA-DR1 Antigen / immunology*
  • HLA-DR1 Antigen / metabolism
  • Humans
  • Immunization
  • Immunodominant Epitopes / chemistry
  • Immunodominant Epitopes / immunology*
  • Immunoglobulin G / immunology
  • Mice
  • Mice, Transgenic
  • Peptide Fragments / chemistry
  • Peptide Fragments / immunology*
  • Peptide Fragments / metabolism
  • Protein Binding / immunology
  • Purpura, Thrombotic Thrombocytopenic / genetics
  • Purpura, Thrombotic Thrombocytopenic / immunology
  • Purpura, Thrombotic Thrombocytopenic / metabolism


  • Epitopes, T-Lymphocyte
  • HLA-DR1 Antigen
  • Immunodominant Epitopes
  • Immunoglobulin G
  • Peptide Fragments
  • ADAMTS13 Protein
  • ADAMTS13 protein, human