Characterization of a Human Platelet Antigen-1a–Specific Monoclonal Antibody Derived from a B Cell from a Woman Alloimmunized in Pregnancy
| Autor: | Bjørn Skogen, Tor B. Stuge, Terje E. Michaelsen, Øistein Ihle, Maria Averina, Mette Kjaer, Anne Husebekk, Gøril Heide, Cedric Ghevaert, Mariana Eksteen, Heidi Tiller |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Blood Platelets
endocrine system Platelet Aggregation medicine.drug_class Molecular Sequence Data Immunology Integrin Antibody Affinity Immunoglobulin Variable Region Monoclonal antibody Flow cytometry Phagocytosis Antibody Specificity Isoantibodies Pregnancy medicine Humans Immunology and Allergy Antigens Human Platelet Platelet Amino Acid Sequence B cell Cell Line Transformed B-Lymphocytes Base Sequence biology medicine.diagnostic_test business.industry Integrin beta3 Antibodies Monoclonal Integrin alphaVbeta3 medicine.disease Molecular biology Recombinant Proteins Human platelet antigen medicine.anatomical_structure Polyclonal antibodies Immunoglobulin G Antibody Formation Mutation Neonatal alloimmune thrombocytopenia biology.protein Female business Immunologic Memory Protein Binding |
| Zdroj: | The Journal of Immunology. 194:5751-5760 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.1401599 |
| Popis: | Human platelet Ag (HPA)-1a, located on integrin β3, is the main target for alloantibodies responsible for fetal and neonatal alloimmune thrombocytopenia (FNAIT) in the white population. There are ongoing efforts to develop an Ab prophylaxis and therapy to prevent or treat FNAIT. In this study, an mAb specific for HPA-1a, named 26.4, was derived from an immortalized B cell from an alloimmunized woman who had an infant affected by FNAIT. It is the only HPA-1a–specific human mAb with naturally paired H and L chains. Specific binding of mAb 26.4, both native and recombinant forms, to platelets and to purified integrins αIIbβ3 (from platelets) and αVβ3 (from trophoblasts) from HPA-1a+ donors was demonstrated by flow cytometry and surface plasmon resonance technology, respectively. No binding to HPA-1a− platelets or integrins was detected. Moreover, the Ab binds with higher affinity to integrin αVβ3 compared with a second HPA-1a–specific human mAb, B2G1. Further in vitro experimentation demonstrated that mAb 26.4 can opsonize HPA-1a+ platelets for enhanced phagocytosis by monocytes, inhibit binding of maternal polyclonal anti–HPA-1a Abs, and weakly inhibit aggregation of HPA-1a–heterozygous platelets, the latter with no predicted clinical relevance. Thus, mAb 26.4 is highly specific for HPA-1a and could potentially be explored for use as a prophylactic or therapeutic reagent for FNAIT intervention and as a phenotyping reagent to identify women at risk for immunization. |
| Databáze: | OpenAIRE |
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