دورية أكاديمية
Individualized VDJ recombination predisposes the available Ig sequence space.
| العنوان: | Individualized VDJ recombination predisposes the available Ig sequence space. |
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| المؤلفون: | Slabodkin A; Department of Immunology and Oslo University Hospital, University of Oslo, 0372 Oslo, Norway., Chernigovskaya M; Department of Immunology and Oslo University Hospital, University of Oslo, 0372 Oslo, Norway., Mikocziova I; Department of Immunology and Oslo University Hospital, University of Oslo, 0372 Oslo, Norway., Akbar R; Department of Immunology and Oslo University Hospital, University of Oslo, 0372 Oslo, Norway., Scheffer L; Department of Informatics, University of Oslo, 0373 Oslo, Norway., Pavlović M; Department of Informatics, University of Oslo, 0373 Oslo, Norway., Bashour H; School of Life Sciences, University of Warwick, Coventry CV4 7AL, United Kingdom., Snapkov I; Department of Immunology and Oslo University Hospital, University of Oslo, 0372 Oslo, Norway., Mehta BB; Department of Immunology and Oslo University Hospital, University of Oslo, 0372 Oslo, Norway., Weber CR; Department of Biosystems Science and Engineering, ETH Zurich, 4058 Basel, Switzerland., Gutierrez-Marcos J; School of Life Sciences, University of Warwick, Coventry CV4 7AL, United Kingdom., Sollid LM; Department of Immunology and Oslo University Hospital, University of Oslo, 0372 Oslo, Norway., Haff IH; Department of Mathematics, University of Oslo, 0371 Oslo, Norway., Sandve GK; Department of Informatics, University of Oslo, 0373 Oslo, Norway., Robert PA; Department of Immunology and Oslo University Hospital, University of Oslo, 0372 Oslo, Norway., Greiff V; Department of Immunology and Oslo University Hospital, University of Oslo, 0372 Oslo, Norway. |
| المصدر: | Genome research [Genome Res] 2021 Dec; Vol. 31 (12), pp. 2209-2224. Date of Electronic Publication: 2021 Nov 23. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cold Spring Harbor Laboratory Press Country of Publication: United States NLM ID: 9518021 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1549-5469 (Electronic) Linking ISSN: 10889051 NLM ISO Abbreviation: Genome Res Subsets: PubMed not MEDLINE; MEDLINE |
| أسماء مطبوعة: | Original Publication: Cold Spring Harbor, N.Y. : Cold Spring Harbor Laboratory Press, c1995- |
| مستخلص: | The process of recombination between variable (V), diversity (D), and joining (J) immunoglobulin (Ig) gene segments determines an individual's naive Ig repertoire and, consequently, (auto)antigen recognition. VDJ recombination follows probabilistic rules that can be modeled statistically. So far, it remains unknown whether VDJ recombination rules differ between individuals. If these rules differed, identical (auto)antigen-specific Ig sequences would be generated with individual-specific probabilities, signifying that the available Ig sequence space is individual specific. We devised a sensitivity-tested distance measure that enables inter-individual comparison of VDJ recombination models. We discovered, accounting for several sources of noise as well as allelic variation in Ig sequencing data, that not only unrelated individuals but also human monozygotic twins and even inbred mice possess statistically distinguishable immunoglobulin recombination models. This suggests that, in addition to genetic, there is also nongenetic modulation of VDJ recombination. We demonstrate that population-wide individualized VDJ recombination can result in orders of magnitude of difference in the probability to generate (auto)antigen-specific Ig sequences. Our findings have implications for immune receptor-based individualized medicine approaches relevant to vaccination, infection, and autoimmunity. (© 2021 Slabodkin et al.; Published by Cold Spring Harbor Laboratory Press.) |
| تواريخ الأحداث: | Date Created: 20211124 Latest Revision: 20231120 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC8647828 |
| DOI: | 10.1101/gr.275373.121 |
| PMID: | 34815307 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1549-5469 |
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| DOI: | 10.1101/gr.275373.121 |