دورية أكاديمية
Poor-Quality Vβ Recombination Signal Sequences and the DNA Damage Response ATM Kinase Collaborate to Establish TCRβ Gene Repertoire and Allelic Exclusion.
| العنوان: | Poor-Quality Vβ Recombination Signal Sequences and the DNA Damage Response ATM Kinase Collaborate to Establish TCRβ Gene Repertoire and Allelic Exclusion. |
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| المؤلفون: | Wu GS; Immunology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; and.; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA., Culberson EJ; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA., Allyn BM; Immunology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; and.; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA., Bassing CH; Immunology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; and bassing@email.chop.edu.; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA. |
| المصدر: | Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2022 Jun 01; Vol. 208 (11), pp. 2583-2592. Date of Electronic Publication: 2022 May 09. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association of Immunologists Country of Publication: United States NLM ID: 2985117R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1550-6606 (Electronic) Linking ISSN: 00221767 NLM ISO Abbreviation: J Immunol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Bethesda, MD : American Association of Immunologists Original Publication: Baltimore : Williams & Wilkins, c1950- |
| مواضيع طبية MeSH: | Protein Sorting Signals*/genetics , Receptors, Antigen, T-Cell, alpha-beta*/genetics, Alleles ; Animals ; DNA Damage ; DNA Repair/genetics ; Gene Rearrangement, beta-Chain T-Cell Antigen Receptor/genetics ; Mice ; V(D)J Recombination/genetics |
| مستخلص: | The monoallelic expression (allelic exclusion) of diverse lymphocyte Ag receptor genes enables specific immune responses. Allelic exclusion is achieved by asynchronous initiation of V(D)J recombination between alleles and protein encoded by successful rearrangement on the first allele signaling permanent inhibition of V rearrangement on the other allele. The ATM kinase that guides DNA repair and transiently suppresses V(D)J recombination also helps impose allelic exclusion through undetermined mechanisms. At the TCRβ locus, one Vβ gene segment ( V31 ) rearranges only by inversion, whereas all other Vβ segments rearrange by deletion except for rare cases in which they rearrange through inversion following V31 rearrangement. The poor-quality recombination signal sequences (RSSs) of V31 and V2 help establish TCRβ gene repertoire and allelic exclusion by stochastically limiting initiation of Vβ rearrangements before TCRβ protein-signaled permanent silencing of Vβ recombination. We show in this study in mice that ATM functions with these RSSs and the weak V1 RSS to shape TCRβ gene repertoire by restricting their Vβ segments from initiating recombination and hindering aberrant nonfunctional Vβ recombination products, especially during inversional V31 rearrangements. We find that ATM collaborates with the V1 and V2 RSSs to help enforce allelic exclusion by facilitating competition between alleles for initiation and functional completion of rearrangements of these Vβ segments. Our data demonstrate that the fundamental genetic DNA elements that underlie inefficient Vβ recombination cooperate with ATM-mediated rapid DNA damage responses to help establish diversity and allelic exclusion of TCRβ genes. (Copyright © 2022 by The American Association of Immunologists, Inc.) |
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| معلومات مُعتمدة: | R01 AI130231 United States AI NIAID NIH HHS; R01 AI143661 United States AI NIAID NIH HHS; T32 AI055428 United States AI NIAID NIH HHS |
| المشرفين على المادة: | 0 (Protein Sorting Signals) 0 (Receptors, Antigen, T-Cell, alpha-beta) |
| تواريخ الأحداث: | Date Created: 20220509 Date Completed: 20220524 Latest Revision: 20230602 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC9133172 |
| DOI: | 10.4049/jimmunol.2100489 |
| PMID: | 35534211 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1550-6606 |
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| DOI: | 10.4049/jimmunol.2100489 |