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

Abstract

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.

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

“…33,34 Briefly, samples were screened in duplicate wells of microtiter plates coated with purified GPIIb/IIIa. Background binding was determined by incubating each sample in uncoated wells, and control samples positive and negative for antibody were also included.…”

Reconsidering fetal and neonatal alloimmune thrombocytopenia with a focus on screening and prevention

“…Shortly before, the same research group demonstrated the proliferation of T cells specifically in response to culturing peripheral blood mononuclear cells from HPA-1a-immunized women with HPA-1a, but not HPA-1b, peptides, supporting the notion that HPA-1a could be a T-cell epitope associated with FNAIT [52]. Later, other groups also demonstrated proliferative responses in peripheral blood mononuclear cells from HPA-1a-immunized women cultured with HPA-1a peptides [53,54]. It was also demonstrated that the proliferating cells were CD4 positive [54].…”

“…Later, other groups also demonstrated proliferative responses in peripheral blood mononuclear cells from HPA-1a-immunized women cultured with HPA-1a peptides [53,54]. It was also demonstrated that the proliferating cells were CD4 positive [54]. Furthermore, it has been demonstrated that a naturally processed epitope containing the HPA-1a polymorphism can be isolated from HLA-DRB3*0101-positive antigen-presenting cells [55].…”

“…In these women, T-cell responses may be driven by other MHC molecules and may be T-cell epitopes derived from alloantigens different from, but still physically linked to, HPA-1a. In fact, one other MHC allele, HLA-DQB1*0201, has also been found to be associated with FNAIT [9,54].…”

T cell responses to human platelet antigen–1a involve a unique form of indirect allorecognition

“…Predictably, targeted manipulation of T cell recognition of the HPA-1a peptide:DRA/ DRB3*01:01 complex could be an effective mean to prevent or to reduce HPA-1a-specific antibody responses and thus prevent FNAIT occurrence. Toward this end, several studies have been aimed at the investigation of HPA-1a-specific T cell responses (13)(14)(15) and antigen processing and presentation (16). Several different CD4 + T cells specific for HPA-1a peptide were clonally isolated in 2 independent studies (7,8).…”