Submitted September 5, 2006
Accepted December 15, 2006
Mapping helper T cell epitopes on platelet membrane glycoprotein IIIa in chronic autoimmune thrombocytopenic purpura
Hosea Sukati, Henry G Watson, Stanislaw J Urbaniak, and Robert N Barker*
Dept of Medicine and Therapeutics, University of Aberdeen, United Kingdom
Department of Haematology, Aberdeen Royal Infirmary, United Kingdom
Academic Transfusion Medicine Unit, Regional Transfusion Centre, Aberdeen, United Kingdom
* Corresponding author; email: r.n.barker{at}abdn.ac.uk.
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 (PBMC) 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 PBMC from 28 of the patients, and, typically, multiple sequences were stimulatory. In contrast, responses in healthy control donors were rare (
2=115.967; p=<0.001). It was confirmed that the proliferating PBMC 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 PBMC from 24 patients (77%) responding to one or more of the four 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.
