Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
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.
View: Text | PDF
Research Article Immunology

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

  • Text
  • PDF
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

×

Figure 3

Peptide binding to the DRA/DRB3ai*01:01-positive cell line STEINLIN.

Options: View larger image (or click on image) Download as PowerPoint
Peptide binding to the DRA/DRB3ai*01:01-positive cell line
             ...
Peptides (12-mers) with single or multiple amino acid substitutions compared with HPA-1a peptide, and extended with a biotinylated linker peptide, were incubated with STEINLIN cells at 5 μM and 10 μM peptide in the presence of 2.5 μM AdEtOH. The efficiency of binding to APCs was assessed by flow cytometry with streptavidin-conjugated R-PE. Binding was measured as percent specific binding (L33 peptide defined as 100%). Each peptide that bound efficiently to STEINLIN was also examined for binding to MHC-matched cell lines DUCAF, EMJ, and EK such that binding to any other MHC class II molecule on STEINLIN could be ruled out. Data points from independent experiments are presented as dots, with bars representing mean ± SEM of at least 3 experiments. Raw data values were median R-PE fluorescence intensity on B-LCLs (gated by light scatter cytogram). Background intensity (cells only, no peptide) was subtracted before calculating the specific binding within each experiment. AdEtOH, adamantane ethanol; APC, antigen-presenting cell; R-PE, R-phycoerythrin; B-LCL, B-lymphoblastoid cell lines

Copyright © 2023 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts