Isolation of monoclonal antibodies from anti-synthetase syndrome patients and affinity maturation by recombination of independent somatic variants
| العنوان: | Isolation of monoclonal antibodies from anti-synthetase syndrome patients and affinity maturation by recombination of independent somatic variants |
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| المؤلفون: | Karine Hervé, Carl L. Hansen, Yeeting E. Chong, Luke Burman, Kaitlyn Rauch, David W Collins, Leslie A. Nangle, Stephanie Pfaffen, Kevin A. Heyries, Anders Klaus, David J. King, Sherie Duncan, Kristina Hamel |
| المصدر: | mAbs article-version (VoR) Version of Record |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | medicine.drug_class, Somatic cell, Immunology, Antibody Affinity, Somatic hypermutation, autoimmune disease, Biology, Monoclonal antibody, medicine.disease_cause, Epitope, Histidine-tRNA Ligase, Affinity maturation, Report, antibody, medicine, Immunology and Allergy, Humans, protein evolution, cellular immune response, Autoantibodies, Genetics, Mutation, Myositis, repertoire, Antibodies, Monoclonal, bioinformatics, single cell, biology.protein, Immunologic Techniques, Somatic Hypermutation, Immunoglobulin, Aminoacyl tRNA synthetase, Antibody, Clone (B-cell biology) |
| الوصف: | The autoimmune disease known as Jo-1 positive anti-synthetase syndrome (ASS) is characterized by circulating antibody titers to histidyl-tRNA synthetase (HARS), which may play a role in modulating the non-canonical functions of HARS. Monoclonal antibodies to HARS were isolated by single-cell screening and sequencing from three Jo-1 positive ASS patients and shown to be of high affinity, covering diverse epitope space. The immune response was further characterized by repertoire sequencing from the most productive of the donor samples. In line with previous studies of autoimmune repertoires, these antibodies tended to have long complementarity-determining region H3 sequences with more positive-charged residues than average. Clones of interest were clustered into groups with related sequences, allowing us to observe different somatic mutations in related clones. We postulated that these had found alternate structural solutions for high affinity binding, but that mutations might be transferable between clones to further enhance binding affinity. Transfer of somatic mutations between antibodies within the same clonal group was able to enhance binding affinity in a number of cases, including beneficial transfer of a mutation from a lower affinity clone into one of higher affinity. Affinity enhancement was seen with mutation transfer both between related single-cell clones, and directly from related repertoire sequences. To our knowledge, this is the first demonstration of somatic hypermutation transfer from repertoire sequences to further mature in vivo derived antibodies, and represents an additional tool to aid in affinity maturation for the development of antibodies. |
| تدمد: | 1942-0870 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5ba2e8472152310fbe9b13f76cb0c9b2Test https://pubmed.ncbi.nlm.nih.gov/33131414Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....5ba2e8472152310fbe9b13f76cb0c9b2 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19420870 |
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