Mapping helper T-cell epitopes on platelet membrane glycoprotein IIIa in chronic autoimmune thrombocytopenic purpura

Hosea M Sukati, Henry G. Watson, Stanislaw Urbaniak, Robert Norman Barker

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Abstract

Chronic autoimmune thrombocytopenic purpura (AITP) is associated with autoantibodies specific for platelet membrane components, often including glycoprotein GPIIIa. T helper (Th) cells reactive with GPIIIa, which are capable of driving the autoantibody response, are activated in AITP, and the aim here was to map the epitopes that they recognize. Peripheral blood mononuclear cells (PBMCs) were obtained from 31 patients with AITP and 30 control donors and stimulated with a panel of 86 overlapping synthetic 15-mer-peptides spanning the complete sequence of GPIIIa. One or more peptides elicited recall proliferation by PBMCs from 28 of the patients, and, typically, multiple sequences were stimulatory. In contrast, responses in healthy control donors were rare (chi-square test = 115.967; P <= .001). It was confirmed that the proliferating PBMCs from patients were cells of the CD3(+)CD4(+) helper phenotype that were MHC class II restricted. Despite variation between different cases of AITP, particular sequences were commonly recognized with PBMCs from 24 patients (77%) responding to 1 or more of the 4 most dominant peptides. Mapping such dominant autoreactive helper epitopes is the first step in the development of new approaches to the treatment of AITP, based on the use of peptides to tolerize Th cells specific for platelet glycoproteins.

Original languageEnglish
Pages (from-to)4528-4538
Number of pages11
JournalBlood
Volume109
Issue number10
Early online date1 Feb 2007
DOIs
Publication statusPublished - 15 May 2007

Keywords

  • rheumatoid-arthritis
  • rhesus polypeptides
  • Japanese patients
  • hemolytic-anemia
  • in-vitro
  • B-cells
  • peptide
  • blood
  • autoantibodies
  • tolerance

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