Comparisons of the antibody repertoires of a humanized rodent and humans by high throughput sequencing
| العنوان: | Comparisons of the antibody repertoires of a humanized rodent and humans by high throughput sequencing |
|---|---|
| المؤلفون: | Bryan Briney, Dennis R. Burton, Collin Joyce |
| المصدر: | Scientific Reports Scientific Reports, Vol 10, Iss 1, Pp 1-9 (2020) |
| بيانات النشر: | Cold Spring Harbor Laboratory, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Genes, Immunoglobulin Heavy Chain, lcsh:Medicine, Datasets as Topic, Somatic hypermutation, Computational biology, Biology, Immunoglobulin light chain, Article, DNA sequencing, 03 medical and health sciences, Immunoglobulin kappa-Chains, 0302 clinical medicine, Species Specificity, Antibody Repertoire, Immunogenetics, Animals, Humans, lcsh:Science, Data mining, Gene, Multidisciplinary, Sequence Homology, Amino Acid, Repertoire, lcsh:R, Genetic Variation, High-Throughput Nucleotide Sequencing, Antibody Diversity, Immunoglobulin Class Switching, V(D)J Recombination, Rats, 030104 developmental biology, Immunoglobulin class switching, Organ Specificity, biology.protein, lcsh:Q, VDJ Exons, Genes, Immunoglobulin Light Chain, Lymph Nodes, Somatic Hypermutation, Immunoglobulin, Rats, Transgenic, Antibody, Sequence Alignment, Software, Spleen, 030215 immunology |
| الوصف: | The humanization of animal model immune systems by genetic engineering has shown great promise for antibody discovery, tolerance studies and for the evaluation of vaccines. Assessment of the baseline antibody repertoires of unimmunized model animals will be useful as a benchmark for future immunization experiments. We characterized the heavy chain and kappa light chain antibody repertoires of a model animal, the OmniRat, by high throughput antibody sequencing and made use of two novel datasets for comparison to human repertoires. Intra-animal and inter-animal repertoire comparisons reveal a high level of conservation in antibody diversity between the lymph node and spleen and between members of the species. Multiple differences were found in both the heavy and kappa chain repertoires between OmniRats and humans including gene segment usage, CDR3 length distributions, class switch recombination, somatic hypermutation levels and in features of V(D)J recombination. The Inference and Generation of Repertoires (IGoR) software tool was used to model recombination in VH regions which allowed for the quantification of some of these differences. Diversity estimates of the OmniRat heavy chain repertoires almost reached that of humans, around two orders of magnitude less. Despite variation between the species repertoires, a high frequency of OmniRat clonotypes were also found in the human repertoire. These data give insights into the development and selection of humanized animal antibodies and provide actionable information for use in vaccine studies. |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::131a387d2607f885dc1e7ff325c2e370Test https://doi.org/10.1101/776385Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....131a387d2607f885dc1e7ff325c2e370 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |