Characterization of the alloreactive helper T-cell response to the platelet membrane glycoprotein IIIa (integrin-ß3) in human platelet antigen-1a alloimmunized human platelet antigen-1b1b women

H. Sukati, H. Bessos, Robert Norman Barker, Stanislaw Urbaniak

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

BACKGROUND: The aims were to characterize the helper T-cell response to platelet (PLT) glycoprotein (GP) IIIa, which stimulates the alloimmune antibody response to human PLT antigen (HPA)-1a, to identify immunodominant epitopes and to examine the HLA Class II associations.

STUDY DESIGN AND METHODS: Peripheral blood mononuclear cells (PBMNCs) were obtained from 21 HPA-1b1b women who had an HPA-1a-mismatched pregnancy, 14 of whom developed anti-HPA-1a, and 11 control donors. PBMNCs were stimulated with two panels of 15-mer peptides corresponding to the HPA-1a/1b polymorphic region, with either Leu(33)(-1a) or Pro(33) (-1b) at each possible position, and the proliferative responses were measured. HLA Class II and HPA genotyping was by conventional polymerase chain reaction-sequence-specific priming.

RESULTS: Peptides with Leu33 at, or near, the C-terminus contained an immunodominant epitope, stimulating proliferation by helper T cells from all nine women who had anti-HPA-1 a at the time of testing; peptide L1 (Val(19)-Leu(33)) stimulated a response in 50 percent of these women. Their T cells did not respond to the corresponding HPA-1b Pro(33) peptides, and responses to either peptide panel were rare in unimmunized women and controls. HLA-DRB3*01+ was significantly overrepresented (p = 0.014) in alloimmunized women whose T cells responded to the major HPA-1a Leu(33)-containing epitope. Conversely, HLA-DRB1*15 was negatively associated (p = 0.014) with this response.

CONCLUSIONS: The HPA-1a polymorphic region of GPIIIa contains both the linear T-cell and the conformational B-cell epitopes. The immunodominant T-cell epitope is constrained by HLA-DRB3*01+, and if presented by a tolerogenic route, a peptide containing this epitope may form the basis for the prevention or reversal of the alloimmune response to HPA-1a.

Original languageEnglish
Pages (from-to)1165-1177
Number of pages12
JournalTransfusion
Volume45
Issue number7
DOIs
Publication statusPublished - Jul 2005

Keywords

  • SEQUENCE-SPECIFIC PRIMERS
  • AUTOIMMUNE ENCEPHALOMYELITIS
  • RHESUS POLYPEPTIDES
  • PEPTIDE BINDING
  • THROMBOCYTOPENIA
  • IDENTIFICATION
  • TOLERANCE
  • EPITOPES
  • DNA
  • LOCALIZATION

Cite this

Characterization of the alloreactive helper T-cell response to the platelet membrane glycoprotein IIIa (integrin-ß3) in human platelet antigen-1a alloimmunized human platelet antigen-1b1b women. / Sukati, H.; Bessos, H.; Barker, Robert Norman; Urbaniak, Stanislaw.

In: Transfusion, Vol. 45, No. 7, 07.2005, p. 1165-1177.

Research output: Contribution to journalArticle

@article{a2700941277741e9825093713b217526,
title = "Characterization of the alloreactive helper T-cell response to the platelet membrane glycoprotein IIIa (integrin-{\ss}3) in human platelet antigen-1a alloimmunized human platelet antigen-1b1b women",
abstract = "BACKGROUND: The aims were to characterize the helper T-cell response to platelet (PLT) glycoprotein (GP) IIIa, which stimulates the alloimmune antibody response to human PLT antigen (HPA)-1a, to identify immunodominant epitopes and to examine the HLA Class II associations.STUDY DESIGN AND METHODS: Peripheral blood mononuclear cells (PBMNCs) were obtained from 21 HPA-1b1b women who had an HPA-1a-mismatched pregnancy, 14 of whom developed anti-HPA-1a, and 11 control donors. PBMNCs were stimulated with two panels of 15-mer peptides corresponding to the HPA-1a/1b polymorphic region, with either Leu(33)(-1a) or Pro(33) (-1b) at each possible position, and the proliferative responses were measured. HLA Class II and HPA genotyping was by conventional polymerase chain reaction-sequence-specific priming.RESULTS: Peptides with Leu33 at, or near, the C-terminus contained an immunodominant epitope, stimulating proliferation by helper T cells from all nine women who had anti-HPA-1 a at the time of testing; peptide L1 (Val(19)-Leu(33)) stimulated a response in 50 percent of these women. Their T cells did not respond to the corresponding HPA-1b Pro(33) peptides, and responses to either peptide panel were rare in unimmunized women and controls. HLA-DRB3*01+ was significantly overrepresented (p = 0.014) in alloimmunized women whose T cells responded to the major HPA-1a Leu(33)-containing epitope. Conversely, HLA-DRB1*15 was negatively associated (p = 0.014) with this response.CONCLUSIONS: The HPA-1a polymorphic region of GPIIIa contains both the linear T-cell and the conformational B-cell epitopes. The immunodominant T-cell epitope is constrained by HLA-DRB3*01+, and if presented by a tolerogenic route, a peptide containing this epitope may form the basis for the prevention or reversal of the alloimmune response to HPA-1a.",
keywords = "SEQUENCE-SPECIFIC PRIMERS, AUTOIMMUNE ENCEPHALOMYELITIS, RHESUS POLYPEPTIDES, PEPTIDE BINDING, THROMBOCYTOPENIA, IDENTIFICATION, TOLERANCE, EPITOPES, DNA, LOCALIZATION",
author = "H. Sukati and H. Bessos and Barker, {Robert Norman} and Stanislaw Urbaniak",
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pages = "1165--1177",
journal = "Transfusion",
issn = "0041-1132",
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number = "7",

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TY - JOUR

T1 - Characterization of the alloreactive helper T-cell response to the platelet membrane glycoprotein IIIa (integrin-ß3) in human platelet antigen-1a alloimmunized human platelet antigen-1b1b women

AU - Sukati, H.

AU - Bessos, H.

AU - Barker, Robert Norman

AU - Urbaniak, Stanislaw

PY - 2005/7

Y1 - 2005/7

N2 - BACKGROUND: The aims were to characterize the helper T-cell response to platelet (PLT) glycoprotein (GP) IIIa, which stimulates the alloimmune antibody response to human PLT antigen (HPA)-1a, to identify immunodominant epitopes and to examine the HLA Class II associations.STUDY DESIGN AND METHODS: Peripheral blood mononuclear cells (PBMNCs) were obtained from 21 HPA-1b1b women who had an HPA-1a-mismatched pregnancy, 14 of whom developed anti-HPA-1a, and 11 control donors. PBMNCs were stimulated with two panels of 15-mer peptides corresponding to the HPA-1a/1b polymorphic region, with either Leu(33)(-1a) or Pro(33) (-1b) at each possible position, and the proliferative responses were measured. HLA Class II and HPA genotyping was by conventional polymerase chain reaction-sequence-specific priming.RESULTS: Peptides with Leu33 at, or near, the C-terminus contained an immunodominant epitope, stimulating proliferation by helper T cells from all nine women who had anti-HPA-1 a at the time of testing; peptide L1 (Val(19)-Leu(33)) stimulated a response in 50 percent of these women. Their T cells did not respond to the corresponding HPA-1b Pro(33) peptides, and responses to either peptide panel were rare in unimmunized women and controls. HLA-DRB3*01+ was significantly overrepresented (p = 0.014) in alloimmunized women whose T cells responded to the major HPA-1a Leu(33)-containing epitope. Conversely, HLA-DRB1*15 was negatively associated (p = 0.014) with this response.CONCLUSIONS: The HPA-1a polymorphic region of GPIIIa contains both the linear T-cell and the conformational B-cell epitopes. The immunodominant T-cell epitope is constrained by HLA-DRB3*01+, and if presented by a tolerogenic route, a peptide containing this epitope may form the basis for the prevention or reversal of the alloimmune response to HPA-1a.

AB - BACKGROUND: The aims were to characterize the helper T-cell response to platelet (PLT) glycoprotein (GP) IIIa, which stimulates the alloimmune antibody response to human PLT antigen (HPA)-1a, to identify immunodominant epitopes and to examine the HLA Class II associations.STUDY DESIGN AND METHODS: Peripheral blood mononuclear cells (PBMNCs) were obtained from 21 HPA-1b1b women who had an HPA-1a-mismatched pregnancy, 14 of whom developed anti-HPA-1a, and 11 control donors. PBMNCs were stimulated with two panels of 15-mer peptides corresponding to the HPA-1a/1b polymorphic region, with either Leu(33)(-1a) or Pro(33) (-1b) at each possible position, and the proliferative responses were measured. HLA Class II and HPA genotyping was by conventional polymerase chain reaction-sequence-specific priming.RESULTS: Peptides with Leu33 at, or near, the C-terminus contained an immunodominant epitope, stimulating proliferation by helper T cells from all nine women who had anti-HPA-1 a at the time of testing; peptide L1 (Val(19)-Leu(33)) stimulated a response in 50 percent of these women. Their T cells did not respond to the corresponding HPA-1b Pro(33) peptides, and responses to either peptide panel were rare in unimmunized women and controls. HLA-DRB3*01+ was significantly overrepresented (p = 0.014) in alloimmunized women whose T cells responded to the major HPA-1a Leu(33)-containing epitope. Conversely, HLA-DRB1*15 was negatively associated (p = 0.014) with this response.CONCLUSIONS: The HPA-1a polymorphic region of GPIIIa contains both the linear T-cell and the conformational B-cell epitopes. The immunodominant T-cell epitope is constrained by HLA-DRB3*01+, and if presented by a tolerogenic route, a peptide containing this epitope may form the basis for the prevention or reversal of the alloimmune response to HPA-1a.

KW - SEQUENCE-SPECIFIC PRIMERS

KW - AUTOIMMUNE ENCEPHALOMYELITIS

KW - RHESUS POLYPEPTIDES

KW - PEPTIDE BINDING

KW - THROMBOCYTOPENIA

KW - IDENTIFICATION

KW - TOLERANCE

KW - EPITOPES

KW - DNA

KW - LOCALIZATION

U2 - 10.1111/j.1537-2995.2005.00188.x

DO - 10.1111/j.1537-2995.2005.00188.x

M3 - Article

VL - 45

SP - 1165

EP - 1177

JO - Transfusion

JF - Transfusion

SN - 0041-1132

IS - 7

ER -