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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