دورية أكاديمية
Healthy Donors Exhibit a CD4 T Cell Repertoire Specific to the Immunogenic Human Hormone H2-Relaxin before Injection.
| العنوان: | Healthy Donors Exhibit a CD4 T Cell Repertoire Specific to the Immunogenic Human Hormone H2-Relaxin before Injection. |
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| المؤلفون: | Azam, Aurélien, Gallais, Yann, Mallart, Sergio, Illiano, Stephane, Duclos, Olivier, Prades, Catherine, Maillère, Bernard |
| المصدر: | Journal of Immunology, 202 (12), 3507-3513 (2019) |
| بيانات النشر: | American Association of Immunologists, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Autoantigens, Epitopes, T-Lymphocyte, HLA-DR Antigens, RLN2 protein, human, Interferon-gamma, Relaxin, Autoantigens/genetics, Autoantigens/immunology, Autoantigens/metabolism, CD4-Positive T-Lymphocytes/physiology, Cell Line, Enzyme-Linked Immunospot Assay, Epitope Mapping, Epitopes, T-Lymphocyte/genetics, Epitopes, T-Lymphocyte/immunology, Epitopes, T-Lymphocyte/metabolism, HLA-DR Antigens/metabolism, Healthy Volunteers, Humans, Immune Tolerance, Interferon-gamma/metabolism, Lymphocyte Activation, Protein Binding, Relaxin/genetics, Relaxin/immunology, Relaxin/metabolism, T-Cell Antigen Receptor Specificity, CD4-Positive T-Lymphocytes, Immunology and Allergy, Immunology, Human health sciences, Immunology & infectious disease, Sciences de la santé humaine, Immunologie & maladie infectieuse |
| الوصف: | H2-relaxin (RLN2) is a two-chain peptide hormone structurally related to insulin with a therapeutic potential in multiple indications. However, multiple injections of human RLN2 induced anti-RLN2 Abs in patients, hampering its clinical development. As T cell activation is required to produce Abs, we wondered whether T cells specific for RLN2 might be already present in the human blood before any injection. We therefore quantified the RLN2-specific T cell repertoire using PBMCs collected from healthy donors. CD4 T cells were stimulated in multiple replicates by weekly rounds of stimulation by dendritic cells loaded with RLN2, and their specificity was assessed by IFN-γ ELISPOT. The number of specific T cell lines was used to estimate the frequency of circulating T cells. In vitro T cell response was demonstrated in 18 of the 23 healthy donors, leading to the generation of 70 independent RLN2-specific T cell lines. The mean frequency of RLN2-specific CD4 T cells was similar to that of T cells specific for known immunogenic therapeutic proteins. Using overlapping peptides, we identified multiple T cell epitopes hosted in the N-terminal parts of the α- and β-chains and common to multiple donors, in agreement with their capacity to bind to multiple HLA-DR molecules. Our results provide important clues to the immunogenicity of RLN2 and highlight the weak central immune tolerance induced against this self-hormone. |
| نوع الوثيقة: | journal article http://purl.org/coar/resource_type/c_6501 article |
| اللغة: | English |
| Relation: | https://syndication.highwire.org/content/doi/10.4049/jimmunol.1800856; urn:issn:0022-1767; urn:issn:1550-6606 |
| DOI: | 10.4049/jimmunol.1800856 |
| URL الوصول: | https://orbi.uliege.be/handle/2268/291138 |
| حقوق: | open access http://purl.org/coar/access_right/c_abf2 info:eu-repo/semantics/openAccess |
| رقم الأكسشن: | edsorb.291138 |
| قاعدة البيانات: | ORBi |
| DOI: | 10.4049/jimmunol.1800856 |
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