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  1. Article ; Online: RSSs set the odds for exclusion.

    Krangel, Michael S

    The Journal of experimental medicine

    2020  Volume 217, Issue 9

    Abstract: In this issue of JEM, Wu et al. (https://doi.org/10.1084/jem.20200412) provide new insights into allelic exclusion. They demonstrate that Vβ-to-DβJβ rearrangement occurs stochastically on two competing Tcrb alleles, with suboptimal Vβ recombination ... ...

    Abstract In this issue of JEM, Wu et al. (https://doi.org/10.1084/jem.20200412) provide new insights into allelic exclusion. They demonstrate that Vβ-to-DβJβ rearrangement occurs stochastically on two competing Tcrb alleles, with suboptimal Vβ recombination signal sequences limiting synchronous rearrangements and essential for allelic exclusion.
    MeSH term(s) Alleles ; Protein Sorting Signals ; Receptors, Antigen, T-Cell, alpha-beta/genetics ; Recombination, Genetic
    Chemical Substances Protein Sorting Signals ; Receptors, Antigen, T-Cell, alpha-beta
    Language English
    Publishing date 2020-06-06
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Comment
    ZDB-ID 218343-2
    ISSN 1540-9538 ; 0022-1007
    ISSN (online) 1540-9538
    ISSN 0022-1007
    DOI 10.1084/jem.20200831
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  2. Article ; Online: RORγt up-regulates RAG gene expression in DP thymocytes to expand the

    Naik, Abani Kanta / Dauphars, Danielle J / Corbett, Elizabeth / Simpson, Lunden / Schatz, David G / Krangel, Michael S

    Science immunology

    2024  Volume 9, Issue 93, Page(s) eadh5318

    Abstract: Recombination activating gene (RAG) expression increases as thymocytes transition from the ... ...

    Abstract Recombination activating gene (RAG) expression increases as thymocytes transition from the CD4
    MeSH term(s) Mice ; Animals ; Thymocytes ; Nuclear Receptor Subfamily 1, Group F, Member 3/genetics ; Receptors, Antigen, T-Cell, alpha-beta ; Transcription Factors/genetics ; Gene Expression
    Chemical Substances Nuclear Receptor Subfamily 1, Group F, Member 3 ; Receptors, Antigen, T-Cell, alpha-beta ; Transcription Factors
    Language English
    Publishing date 2024-03-15
    Publishing country United States
    Document type Journal Article
    ISSN 2470-9468
    ISSN (online) 2470-9468
    DOI 10.1126/sciimmunol.adh5318
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  3. Article ; Online: E protein binding at the

    Mihai, Ariana / Roy, Sumedha / Krangel, Michael S / Zhuang, Yuan

    Frontiers in immunology

    2023  Volume 14, Page(s) 1188738

    Abstract: V(D)J recombination of antigen receptor loci is a highly developmentally regulated process. During T lymphocyte development, recombination of ... ...

    Abstract V(D)J recombination of antigen receptor loci is a highly developmentally regulated process. During T lymphocyte development, recombination of the
    MeSH term(s) Protein Binding ; Receptors, Antigen, T-Cell, alpha-beta/genetics ; Thymocytes ; V(D)J Recombination/genetics ; Transcription Factors/genetics ; Enhancer Elements, Genetic
    Chemical Substances Receptors, Antigen, T-Cell, alpha-beta ; Transcription Factors
    Language English
    Publishing date 2023-07-06
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2023.1188738
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  4. Article: The Ties that Bind (the Igh Locus).

    Krangel, Michael S

    Trends in genetics : TIG

    2016  Volume 32, Issue 5, Page(s) 253–255

    Abstract: Immunoglobulin heavy-chain locus V(D)J recombination requires a 3D chromatin organization which permits widely distributed variable (V) gene segments to contact distant diversity (D) and joining (J) gene segments. A recent study has identified key nodes ... ...

    Abstract Immunoglobulin heavy-chain locus V(D)J recombination requires a 3D chromatin organization which permits widely distributed variable (V) gene segments to contact distant diversity (D) and joining (J) gene segments. A recent study has identified key nodes in the locus interactome, paving the way for new molecular insights into how the locus is configured for recombination.
    Language English
    Publishing date 2016-05
    Publishing country England
    Document type Journal Article
    ZDB-ID 619240-3
    ISSN 1362-4555 ; 0168-9525 ; 0168-9479
    ISSN (online) 1362-4555
    ISSN 0168-9525 ; 0168-9479
    DOI 10.1016/j.tig.2016.03.003
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  5. Article ; Online: Beyond Hypothesis: Direct Evidence That V(D)J Recombination Is Regulated by the Accessibility of Chromatin Substrates.

    Krangel, Michael S

    Journal of immunology (Baltimore, Md. : 1950)

    2015  Volume 195, Issue 11, Page(s) 5103–5105

    MeSH term(s) Chromatin/metabolism ; V(D)J Recombination
    Chemical Substances Chromatin
    Language English
    Publishing date 2015-12-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3056-9
    ISSN 1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
    ISSN (online) 1550-6606
    ISSN 0022-1767 ; 1048-3233 ; 1047-7381
    DOI 10.4049/jimmunol.1502150
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  6. Article ; Online: Methods for Study of Mouse T Cell Receptor α and β Gene Rearrangements.

    Dauphars, Danielle J / Wu, Glendon / Bassing, Craig H / Krangel, Michael S

    Methods in molecular biology (Clifton, N.J.)

    2022  Volume 2580, Page(s) 261–282

    Abstract: Quantitative real-time PCR and next-generation sequencing (NGS) are invaluable techniques to analyze T cell receptor (Tcr) gene rearrangements in mouse lymphocyte populations. Although these approaches are powerful, they also have limitations that must ... ...

    Abstract Quantitative real-time PCR and next-generation sequencing (NGS) are invaluable techniques to analyze T cell receptor (Tcr) gene rearrangements in mouse lymphocyte populations. Although these approaches are powerful, they also have limitations that must be accounted for in experimental design and data interpretation. Here, we provide relevant background required for understanding these limitations and then outline established quantitative real-time PCR and NGS methods that can be used for analysis of mouse Tcra and Tcrb gene rearrangements in mice.
    MeSH term(s) Mice ; Animals ; Receptors, Antigen, T-Cell, alpha-beta/genetics ; Gene Rearrangement ; Polymerase Chain Reaction
    Chemical Substances Receptors, Antigen, T-Cell, alpha-beta
    Language English
    Publishing date 2022-11-14
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-2740-2_16
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  7. Article: Diversification of the TCR β Locus V

    Chen, Shiwei / Krangel, Michael S

    ImmunoHorizons

    2018  Volume 2, Issue 11, Page(s) 377–383

    Abstract: The architectural protein CTCF regulates the conformation and recombination of antigen receptor loci. To study the importance of CTCF ... ...

    Abstract The architectural protein CTCF regulates the conformation and recombination of antigen receptor loci. To study the importance of CTCF in
    Language English
    Publishing date 2018-12-24
    Publishing country United States
    Document type Journal Article
    ISSN 2573-7732
    ISSN 2573-7732
    DOI 10.4049/immunohorizons.1800072
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  8. Article ; Online: Trav15-dv6 family Tcrd rearrangements diversify the Tcra repertoire.

    Dauphars, Danielle J / Mihai, Ariana / Wang, Liuyang / Zhuang, Yuan / Krangel, Michael S

    The Journal of experimental medicine

    2021  Volume 219, Issue 2

    Abstract: The Tcra repertoire is generated by multiple rounds of Vα-Jα rearrangement. However, Tcrd recombination precedes Tcra recombination within the complex Tcra-Tcrd locus. Here, by ablating Tcrd recombination, we report that Tcrd rearrangement broadens ... ...

    Abstract The Tcra repertoire is generated by multiple rounds of Vα-Jα rearrangement. However, Tcrd recombination precedes Tcra recombination within the complex Tcra-Tcrd locus. Here, by ablating Tcrd recombination, we report that Tcrd rearrangement broadens primary Vα use to diversify the Tcra repertoire in mice. We reveal that use of Trav15-dv6 family V gene segments in Tcrd recombination imparts diversity in the Tcra repertoire by instigating use of central and distal Vα segments. Moreover, disruption of the regions containing these genes and their cis-regulatory elements identifies the Trav15-dv6 family as being responsible for driving central and distal Vα recombinations beyond their roles as substrates for Tcrd recombination. Our study demonstrates an indispensable role for Tcrd recombination in general, and the Trav15-dv6 family in particular, in the generation of a combinatorially diverse Tcra repertoire.
    MeSH term(s) Animals ; Female ; Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor ; High-Throughput Nucleotide Sequencing ; Mice ; Mice, Knockout ; Receptors, Antigen, T-Cell, alpha-beta/genetics ; Receptors, Antigen, T-Cell, gamma-delta/genetics ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism ; Thymocytes/immunology ; Thymocytes/metabolism ; V(D)J Recombination
    Chemical Substances Receptors, Antigen, T-Cell, alpha-beta ; Receptors, Antigen, T-Cell, gamma-delta
    Language English
    Publishing date 2021-12-15
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 218343-2
    ISSN 1540-9538 ; 0022-1007
    ISSN (online) 1540-9538
    ISSN 0022-1007
    DOI 10.1084/jem.20211581
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  9. Article ; Online: Immunology at Duke: 2011.

    Krangel, Michael S

    Immunologic research

    2010  Volume 49, Issue 1-3, Page(s) 1–2

    MeSH term(s) Academic Medical Centers ; Immune System Phenomena ; Periodicals as Topic ; Signal Transduction
    Language English
    Publishing date 2010-11-30
    Publishing country United States
    Document type Comment ; Editorial ; Introductory Journal Article
    ZDB-ID 632857-x
    ISSN 1559-0755 ; 0257-277X
    ISSN (online) 1559-0755
    ISSN 0257-277X
    DOI 10.1007/s12026-010-8198-2
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  10. Article ; Online: Chromatin Dynamics and the Development of the TCRα and TCRδ Repertoires.

    Carico, Zachary / Krangel, Michael S

    Advances in immunology

    2015  Volume 128, Page(s) 307–361

    Abstract: The adaptive immune system allows vertebrates to orchestrate highly specific responses to a virtually unlimited milieu of antigens. Effective adaptive immune responses depend on the capacity of T and B lymphocytes to generate diverse repertoires of ... ...

    Abstract The adaptive immune system allows vertebrates to orchestrate highly specific responses to a virtually unlimited milieu of antigens. Effective adaptive immune responses depend on the capacity of T and B lymphocytes to generate diverse repertoires of antigen receptors through the recombination of variable (V), diversity (D), and joining (J) gene segments at antigen receptor loci. V(D)J recombination must be carefully regulated during the early stages of T and B lymphocyte development to ensure the proper development of lymphocyte subsets and to maximize antigen receptor combinatorial diversity. Among all T cell receptor (TCR) and immunoglobulin loci, the TCRα/δ (Tcra/Tcrd) locus is unique in its complexity since it undergoes recombination at two distinct stages of T cell development to create distinct TCR proteins that are used by different lineages of T cells. Here, we review the mechanisms that regulate V(D)J recombination at the Tcra/Tcrd locus, with a focus on the dynamic chromatin environment and how it instructs the assembly of the Tcra and Tcrd repertoires. We discuss the dynamics of Tcra and Tcrd repertoire formation in the context of T cell development, and we consider how the recombination program is directed by localized changes in chromatin structure that regulate the accessibility of Tcra and Tcrd gene segments to the V(D)J recombinase. We then move beyond local to address spatial relationships in the nucleus, emphasizing the three-dimensional organization of the Tcra/Tcrd locus as a critical player in understanding long-distance interactions between chromatin regulatory elements as well as long-distance interactions between recombination substrates.
    MeSH term(s) Animals ; Chromatin Assembly and Disassembly ; Enhancer Elements, Genetic ; Genes, T-Cell Receptor alpha ; Genes, T-Cell Receptor delta ; Humans ; T-Lymphocytes/cytology ; T-Lymphocytes/metabolism ; Transcription, Genetic ; V(D)J Recombination
    Language English
    Publishing date 2015
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 80226-8
    ISSN 1557-8445 ; 0065-2776
    ISSN (online) 1557-8445
    ISSN 0065-2776
    DOI 10.1016/bs.ai.2015.07.005
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