Reactivity of T cells from women with antibodies to the human platelet antigen (HPA)-1a to peptides encompassing the HPA-1 polymorphism

Abstract

SummaryThe human platelet antigen-1a (HPA-1a) is the most common alloantigenic target in fetal and neonatal alloimmune thrombocytopenia (NAIT). Treatment currently depends on the outcome in previous pregnancies. HPA-1 specific T cell responses were determined in 14 HPA-1a alloimmunized women during or after pregnancies affected by NAIT. Peripheral blood mononuclear cells were incubated with peptides encompassing the Leu33Pro polymorphism (residues 20-39 and 24-45 in both Leu33 (HPA-1a) and Pro33 (HPA1b) forms) or control recall antigens in the presence of autologous sera and T cell proliferation was measured by 3 H-thymidine incorporation. Control antenatal and postpartum sera suppressed T cell proliferation and use of such sera was avoided. Most patients (86%) responded to the HPA-1a peptides with 64% also having weaker T cell proliferation to the HPA-1b peptides; 14% had no activity towards any peptide despite responding to control antigens. Administration of IVIG during pregnancy appeared to reduce T cell reactivity to HPA-1 peptides. Postnatal anti-HPA-1a T cell responses from women who had a severe history of NAIT (an intracranial haemorrhage in a previous fetus) were greater than those from women with a mild history. This assay may have the potential to predict disease severity if performed prior to or early in pregnancy.

T-cell responses associated with neonatal alloimmune thrombocytopenia: isolation of HPA-1a–specific, HLA-DRB3*0101–restricted CD4+ T cells

“…Previous reports have provided considerable support to the notion that HPA-1a-specific T cells are present in [17][18][19] In the study published by Maslanka et al, 18 the investigators used TCR spectratyping and PCR techniques with clonotypic primers to track T cells growing in these cultures stimulated with a peptide containing the HPA-1a epitope. The clonotypic primers were also used to show the presence of these T cells in PBMCs at various time points in relation to pregnancy and in platelet-stimulated cultures.…”

Evidence for the Specificity for Platelet HPA-1a Alloepitope and the Presenting HLA-DR52a of Diverse Antigen-Specific Helper T Cell Clones from Alloimmunized Mothers

“…HLA-DR52a was significantly overrepresented in these alloimmunized responders (3), but T cells were not cloned. Jackson et al have recently shown responses to HPA-1a peptides 24 -45 and 20 -39 in bulk PBMC cultures in 21% of alloimmunized mothers, but also to the 1b peptide or the 1a and the 1b peptides simultaneously (34).…”

Low‐dose prednisone and immunoglobulin G treatment for woman at risk for neonatal alloimmune thrombocytopenia and T helper 1 immunity

“…8 Human platelet antigen (HPA) is located on cell membrane glycoproteins, and HPA-1 antigen is most commonly affected with FNAIT (80%). [10][11][12][13] It has been reported that maternal T cell clones associated with FNAIT recognize an integrin beta-3 epitope, which is anchored to the HLA-DRB3 *0101-encoded MHC molecule DR52a. A woman with antigen negative (HPA 1b/1b) is at risk when she has a partner with antigen positive either homozygous (HPA 1a/1a) or heterozygous (HPA 1a/1b).…”