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T cell responses to human platelet antigen–1a involve a unique form of indirect allorecognition
Maria Therese Ahlen, … , Bjørn Skogen, Tor Brynjar Stuge
Maria Therese Ahlen, … , Bjørn Skogen, Tor Brynjar Stuge
Published September 8, 2016
Citation Information: JCI Insight. 2016;1(14):e86558. https://doi.org/10.1172/jci.insight.86558.
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Research Article Immunology

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

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Abstract

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a pregnancy-related condition caused by maternal antibodies binding an alloantigen on fetal platelets. In most cases the alloantigen is formed by a single amino acid, integrin β3 Leu33, referred to as human platelet antigen–1a (HPA-1a). Production of anti–HPA-1a antibodies likely depends on CD4+ T cells that recognize the same alloantigen in complex with the HLA-DRA/DRB3*01:01 molecule. While this complex is well characterized, T cell recognition of it is not. Here, to examine the nature of antigen recognition by HPA-1a–specific T cells, we assayed native and synthetic variants of the integrin β3 peptide antigen for binding to DRA/DRB3*01:01-positive antigen-presenting cells and for T cell activation. We found that HPA-1a–specific T cells recognize non-allogeneic integrin β3 residues anchored to DRA/DRB3*01:01 by the allogeneic Leu33, which itself is not directly recognized by these T cells. Furthermore, these T cell responses are diverse, with different T cells depending on different residues for recognition. This represents a unique form of indirect allorecognition in which a non-allogeneic peptide sequence becomes immunogenic by stable anchoring to MHC by an allogeneic residue.

Authors

Maria Therese Ahlen, Anne Husebekk, Ida Løken Killie, Bjørn Skogen, Tor Brynjar Stuge

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Figure 4

Peptide binding is dose dependent.

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Peptide binding is dose dependent.
Binding of control 12-mer peptides (l...
Binding of control 12-mer peptides (linker only, L33, and P33) to HLA-DRB3*01:01-positive APCs (D4BL4), measured by flow cytometry after peptide pulsing with AdEtOH as MLE. No increase was seen with linker only, while an increase can be seen with L33, LolP1, and P33. Experiments were conducted twice with two replicates; representative histograms are shown. AdEtOH, adamantane ethanol; APC, antigen-presenting cell; MLE, MHC-loading enhancer.

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