ArticleBlood2012
CD4+ T-cell epitopes associated with antibody responses after intravenously and subcutaneously applied human FVIII in humanized hemophilic E17 HLA-DRB1*1501 mice.
Article in Blood, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
What it found
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The trial behind it
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Who cites it
44 citing papers in PubMed, 73 citations in OpenAlex.
- Trial
- Nanoparticles targeting liver sinusoidal endothelial cells improve tolerance to vector and transgene antigens through tolerance spreading.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Regulation of immune responses to therapeutic factor VIII by transplacental delivery of Fc-fused immunodominant factor VIII domains or peptides.Haematologica · 2025Article
- The T follicular helper/T follicular helper regulatory pathway in FVIII immune responses in mice.Blood · 2025Article
- Exploration of biomarkers for inhibitor development in persons with hemophilia A.Research and practice in thrombosis and haemostasis · 2025Article
- MHC class II presentation of FVIII-AnnexinA5 fusion proteins internalized by antigen presenting cells.Frontiers in immunology · 2025Article
- Rational design of FVIII sialylated peptides to target Siglec-3 and Siglec-9 and improve peptide formulations for reverse vaccines.Frontiers in bioengineering and biotechnology · 2025Article
- The use of Bacillus subtilis as a cost-effective expression system for production of Cholera Toxin B fused factor VIII epitope regions applicable for inducing oral immune tolerance.Folia microbiologica · 2024Article
- Article
- Antigen-specific immunotherapy with apitopes suppresses generation of FVIII inhibitor antibodies in HLA-transgenic mice.Blood advances · 2022Article
- Modulating the microenvironment during FVIII uptake influences the nature of FVIII-peptides presented by antigen-presenting cells.Frontiers in immunology · 2022Article
- Neutralizing Antibodies Against Factor VIII Can Occur Through a Non-Germinal Center Pathway.Frontiers in immunology · 2022Article
- A Deep Insight Into Regulatory T Cell Metabolism in Renal Disease: Facts and Perspectives.Frontiers in immunology · 2022Review
- Development of a novel fully functional coagulation factor VIII with reduced immunogenicity utilizing an in silico prediction and deimmunization approach.Journal of thrombosis and haemostasis : JTH · 2021Article
- Induction of Tolerance to Therapeutic Proteins With Antigen-Processing Independent T Cell Epitopes: Controlling Immune Responses to Biologics.Frontiers in immunology · 2021Review
- Identification of Human Antigen-Specific CD4+ Cells with Peptide-MHC Multimer Technologies.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Minimal Essential Human Factor VIII Alterations Enhance Secretion and Gene Therapy Efficiency.Molecular therapy. Methods & clinical development · 2020Article
- Identification of Key Coagulation Activity Determining Elements in Canine Factor VIII.Molecular therapy. Methods & clinical development · 2020Article
- Specificity of the T Cell Response to Protein Biopharmaceuticals.Frontiers in immunology · 2020Review
- Platelet-Targeted FVIII Gene Therapy Restores Hemostasis and Induces Immune Tolerance for Hemophilia A.Frontiers in immunology · 2020Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
Abstract
Today it is generally accepted that B cells require cognate interactions with CD4(+) T cells to develop high-affinity antibodies against proteins. CD4(+) T cells recognize peptides (epitopes) presented by MHC class II molecules that are expressed on antigen-presenting cells. Structural features of both the MHC class II molecule and the peptide determine the specificity of CD4(+) T cells that can bind to the MHC class II-peptide complex. We used a new humanized hemophilic mouse model to identify FVIII peptides presented by HLA-DRB1*1501. This model carries a knockout of all murine MHC class II molecules and expresses a chimeric murine-human MHC class II complex that contains the peptide-binding sites of the human HLA-DRB1*1501. When mice were treated with human FVIII, the proportion of mice that developed antibodies depended on the application route of FVIII and the activation state of the innate immune system. We identified 8 FVIII peptide regions that contained CD4(+) T-cell epitopes presented by HLA-DRB1*1501 to CD4(+) T cells during immune responses against FVIII. CD4(+) T-cell responses after intravenous and subcutaneous application of FVIII involved the same immunodominant FVIII epitopes. Interestingly, most of the 8 peptide regions contained promiscuous epitopes that bound to several different HLA-DR proteins in in vitro binding assays.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.