Cellular responses in FNAIT

The project involves studies of anti-HPA-1a-specific CD4 T cells from alloimmunized women and characterization of the reactivity of their anti-HPA-1a-specific antibodies. There is a single amino acid difference between the maternal and fetal platelet protein variant, however this amino acid is essential for peptide binding to the HLA class II molecule associated with FNAIT. We are investigating the role for these HPA-1a-specific T cells and their characteristics. The project further make us of designed and recombinantly produced proteins to investigate antibody binding characteristics.

Alloreactive CD4+ helper T cells recognize the HPA-1a peptide presented in the DRA/DRB3*01:01 molecule. This may stimulate the anti-HPA-1a-specific B cells and subsequently induce plasma cells to generate anti-HPA-1a antibodies that can target the fetal antigens. Figure created with Biorender.com. 

Previous publications related to this project from our group: 

The prevalence of HPA-1a alloimmunization and the potential risk of FNAIT depend on both the DRB3*01:01 allele and associated DR-DQ haplotypes. Ahlen MT, Heide G, Husebekk A, Skogen B, Kjeldsen-Kragh J, Stuge TB. Scand J Immunol. 2020;92(1):e12890. https://doi.org/10.1111/sji.12890 

T cell responses to Human Platelet Antigen-1a involve a unique form of indirect allorecognition. Ahlen MT, Husebekk A, Killie IL, Skogen B, Stuge TB. JCI Insight. 2016;1(14):e86558 http://doi.org/10.1172/jci.insight.86558

T-cell responses associated with neonatal alloimmune thrombocytopenia: isolation of HPA-1a-specific, HLA-DRB3*0101-restricted CD4+ T cells. Ahlen MT, Husebekk A, Killie MK, Skogen B and Stuge TB. Blood. 2009;16;113(16):3838-3844. https://doi.org/10.1182/blood-2008-09-178475

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