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Tytuł pozycji:

Comparisons of the antibody repertoires of a humanized rodent and humans by high throughput sequencing.

Tytuł:
Comparisons of the antibody repertoires of a humanized rodent and humans by high throughput sequencing.
Autorzy:
Joyce C; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.; Center for Viral Systems Biology, The Scripps Research Institute, La Jolla, CA, USA.
Burton DR; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA. .; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, USA. .; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA. .; Human Vaccines Project, New York, NY, USA. .; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA. .
Briney B; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA. .; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, USA. .; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA. .; Human Vaccines Project, New York, NY, USA. .; Center for Viral Systems Biology, The Scripps Research Institute, La Jolla, CA, USA. .
Źródło:
Scientific reports [Sci Rep] 2020 Jan 24; Vol. 10 (1), pp. 1120. Date of Electronic Publication: 2020 Jan 24.
Typ publikacji:
Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Język:
English
Imprint Name(s):
Original Publication: London : Nature Publishing Group, copyright 2011-
MeSH Terms:
Genes, Immunoglobulin Heavy Chain*
Genes, Immunoglobulin Light Chain*
High-Throughput Nucleotide Sequencing*
Rats, Transgenic/*genetics
Animals ; Datasets as Topic ; Genetic Variation ; Humans ; Immunoglobulin Class Switching ; Immunoglobulin kappa-Chains/genetics ; Lymph Nodes/metabolism ; Organ Specificity ; Rats ; Rats, Transgenic/immunology ; Sequence Alignment ; Sequence Homology, Amino Acid ; Software ; Somatic Hypermutation, Immunoglobulin ; Species Specificity ; Spleen/metabolism ; V(D)J Recombination ; VDJ Exons/genetics
References:
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Grant Information:
U19 AI135995 United States AI NIAID NIH HHS; UM1 AI144462 United States AI NIAID NIH HHS
Substance Nomenclature:
0 (Immunoglobulin kappa-Chains)
Entry Date(s):
Date Created: 20200126 Date Completed: 20201120 Latest Revision: 20240214
Update Code:
20240214
PubMed Central ID:
PMC6981180
DOI:
10.1038/s41598-020-57764-7
PMID:
31980672
Czasopismo naukowe
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.
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