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Characterization of the alloreactive helper T‐cell response to the platelet membrane glycoprotein IIIa (integrin‐β3) in human platelet antigen‐1a alloimmunized human platelet antigen‐1b1b women
Author(s) -
Sukati Hosea,
Bessos Hagop,
Barker Robert N.,
Urbaniak Stanislaw J.
Publication year - 2005
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/j.1537-2995.2005.00188.x
Subject(s) - epitope , immunology , human leukocyte antigen , antigen , priming (agriculture) , neonatal alloimmune thrombocytopenia , t cell , platelet , peripheral blood mononuclear cell , platelet membrane glycoprotein , antibody , biology , microbiology and biotechnology , immune system , pregnancy , biochemistry , in vitro , fetus , botany , germination , genetics
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 Leu 33 at, or near, the C‐terminus contained an immunodominant epitope, stimulating proliferation by helper T cells from all nine women who had anti‐HPA‐1a 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.