V(D)J recombination: how to tame a transposase.

Abstract:

:Since the discovery that the recombination-activating gene (RAG) proteins were capable of transposition in vitro, investigators have been trying to uncover instances of transposition in vivo and understand how this transposase has been harnessed to do useful work while being inhibited from causing deleterious chromosome rearrangements. How to preserve the capacity of the recombinase to promote a certain class of rearrangements while curtailing its ability to catalyze others is an interesting problem. In this review, we examine the progress that has been made toward understanding the regulatory mechanisms that prohibit transposition in order to formulate a model that takes into account the diverse observations that have been made over the last 15 years. First, we touch on the striking mechanistic similarities between transposition and V(D)J recombination and review evidence suggesting that the RAG proteins may be members of the retroviral integrase superfamily. We then dispense with an old theory that certain standard products of V(D)J recombination called signal joints protect against deleterious transposition events. Finally, we discuss the evidence that target capture could serve a regulatory role and close with an analysis of hairpins as preferred targets for RAG-mediated transposition. These novel strategies for harnessing the RAG transposase not only shed light on V(D)J recombination but also may provide insight into the regulation of other transposases.

journal_name

Immunol Rev

journal_title

Immunological reviews

authors

Brandt VL,Roth DB

doi

10.1111/j.0105-2896.2004.00161.x

keywords:

subject

Has Abstract

pub_date

2004-08-01 00:00:00

pages

249-60

eissn

0105-2896

issn

1600-065X

pii

IMR161

journal_volume

200

pub_type

杂志文章,评审
  • E3 ubiquitin ligases Pellinos as regulators of pattern recognition receptor signaling and immune responses.

    abstract::Pellinos are a family of E3 ubiquitin ligases discovered for their role in catalyzing K63-linked polyubiquitination of Pelle, an interleukin-1 (IL-1) receptor-associated kinase homolog in the Drosophila Toll pathway. Subsequent studies have revealed the central and non-redundant roles of mammalian Pellino-1, Pellino-2...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1111/imr.12298

    authors: Medvedev AE,Murphy M,Zhou H,Li X

    更新日期:2015-07-01 00:00:00

  • Chemokines in the systemic organization of immunity.

    abstract::Directed cellular migrations underlie immune system organization. Chemokines and their receptors (along with surface-adhesion molecules) are central to these migrations, targeting developing and mature leukocytes to tissues and microenvironments suitable for their differentiation and function. The chemokine CXCL12 and...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1034/j.1600-065x.2003.00067.x

    authors: Campbell DJ,Kim CH,Butcher EC

    更新日期:2003-10-01 00:00:00

  • The immunobiology of Th1 polarization in high-pathology schistosomiasis.

    abstract::Schistosomiasis is a serious global helminthic disease, in which the main immunopathology consists of a granulomatous and fibrosing reaction against tissue-trapped parasite eggs. The severity of this inflammatory process, the product of a CD4(+) T-cell-mediated immune response against parasite egg antigens, is, howeve...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1111/j.0105-2896.2004.00197.x

    authors: Stadecker MJ,Asahi H,Finger E,Hernandez HJ,Rutitzky LI,Sun J

    更新日期:2004-10-01 00:00:00

  • CD8+ T-cell memory in tumor immunology and immunotherapy.

    abstract::The cellular and molecular mechanisms underlying the formation of distinct central, effector, and exhausted CD8+ T-cell memory subsets were first described in the setting of acute and chronic viral diseases. The role of these T-cell memory subsets are now being illuminated as relevant to the tumor-bearing state. The g...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1111/j.0105-2896.2006.00391.x

    authors: Klebanoff CA,Gattinoni L,Restifo NP

    更新日期:2006-06-01 00:00:00

  • Live or let die: posttranscriptional gene regulation in cell stress and cell death.

    abstract::Studies of the regulation of gene expression historically focused on transcription. However, during stress and apoptosis, profound gene expression changes occur more rapidly and globally than is possible by regulating transcription. Posttranscriptional changes in mRNA processing and translation in response to diverse ...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1111/imr.12052

    authors: Thomas MP,Lieberman J

    更新日期:2013-05-01 00:00:00

  • Immunity to gastrointestinal nematodes: mechanisms and myths.

    abstract::Immune responses to gastrointestinal nematodes have been studied extensively for over 80 years and intensively investigated over the last 30-40 years. The use of laboratory models has led to the discovery of new mechanisms of protective immunity and made major contributions to our fundamental understanding of both inn...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1111/imr.12188

    authors: Grencis RK,Humphreys NE,Bancroft AJ

    更新日期:2014-07-01 00:00:00

  • Evolution of the mammalian MHC: natural selection, recombination, and convergent evolution.

    abstract::The genes that encode molecules involved in antigen presentation within the class I and class II regions of the mammalian major histocompatibility complex (MHC) include several that are highly polymorphic. There is evidence that this polymorphism is maintained by positive selection, most likely overdominant selection,...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1111/j.1600-065x.1999.tb01381.x

    authors: Yeager M,Hughes AL

    更新日期:1999-02-01 00:00:00

  • Determining the immune mechanisms of protection from AIDS: correlates of immunity and the development of syngeneic macaques.

    abstract::The AIDS pandemic is a global emergency and a preventive vaccine is urgently needed. CD4 and CD8 T-cell responses appear important in controlling human immunodeficiency virus (HIV)-1 in humans and simian immunodeficiency virus (SIV) in macaques. The utility of vaccines that induce high levels of SIV- or HIV-specific T...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1034/j.1600-065x.2001.1830108.x

    authors: Kent SJ,Ada GL,Hayes E,Lewis IM

    更新日期:2001-10-01 00:00:00

  • The role of genetically-determined primary alterations of the target organ in the development of spontaneous autoimmune thyroiditis in obese strain (OS) chickens.

    abstract::Immunologists working in the field of autoimmunity tend to concentrate all their efforts on the elucidation of possible malfunctions of the immune system, particularly pathologic changes of immune regulation. Also in the OS model various groups of investigators emphasized this approach, although it was already clear e...

    journal_title:Immunological reviews

    pub_type: 杂志文章

    doi:10.1111/j.1600-065x.1986.tb01167.x

    authors: Wick G,Hála K,Wolf H,Ziemiecki A,Sundick RS,Stöffler-Meilicke M,DeBaets M

    更新日期:1986-12-01 00:00:00

  • The impact of ancestral tetraploidy on antibody heterogeneity in salmonid fishes.

    abstract::The immunoglobulin heavy chain locus in teleost fish is structurally similar to that in mammals, comprising a series of variable gene segments upstream of two constant region genes coding for IgM and IgD. Atlantic salmon have been shown to possess two distinct heavy chain loci, related to the tetraploid ancestry of th...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1111/j.1600-065x.1998.tb01260.x

    authors: Hordvik I

    更新日期:1998-12-01 00:00:00

  • Neuroendocrine regulation of innate lymphoid cells.

    abstract::The activities of the immune system in repairing tissue injury and combating pathogens were long thought to be independent of the nervous system. However, a major regulatory role of immunomodulatory molecules released locally or systemically by the neuroendocrine system has recently emerged. A number of observations a...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1111/imr.12707

    authors: Quatrini L,Vivier E,Ugolini S

    更新日期:2018-11-01 00:00:00

  • The intra- and extracellular functions of ASC specks.

    abstract::Inflammasomes are the central signaling hubs of the inflammatory response. They process cytosolic evidence of infection, cell damage, or metabolic disturbances, and elicit a pro-inflammatory response mediated by members of the interleukin-1 family of cytokines and pyroptotoic cell death. On the molecular level, this i...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1111/imr.12611

    authors: Franklin BS,Latz E,Schmidt FI

    更新日期:2018-01-01 00:00:00

  • Role of microRNAs and long-non-coding RNAs in CD4(+) T-cell differentiation.

    abstract::CD4(+) T lymphocytes orchestrate adaptive immune responses by differentiating into various subsets of effector T cells such as T-helper 1 (Th1), Th2, Th17, and regulatory T cells. These subsets have been generally described by master transcription factors that dictate the expression of cytokines and receptors, which u...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1111/imr.12055

    authors: Pagani M,Rossetti G,Panzeri I,de Candia P,Bonnal RJ,Rossi RL,Geginat J,Abrignani S

    更新日期:2013-05-01 00:00:00

  • T-cell costimulatory pathways in allograft rejection and tolerance.

    abstract::The destiny of activated T cells is critical to the ultimate fate of immune response. After encountering antigen, naïve T cells receive signal 1 through the T-cell receptor (TCR)-major histocompatibility complex (MHC) plus antigenic peptide complex and signal 2 through "positive" costimulatory molecules leading to ful...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1046/j.1600-065x.2003.00088.x

    authors: Rothstein DM,Sayegh MH

    更新日期:2003-12-01 00:00:00

  • Human CD8+ intraepithelial lymphocytes: a unique model to study the regulation of effector cytotoxic T lymphocytes in tissue.

    abstract::The epithelium of the human small intestine contains a large population of intraepithelial cytolytic alphabeta T-cell receptor (TCR) CD8 alpha beta T lymphocytes (IE-CTLs), whose main role is to sustain epithelial integrity by rapidly eliminating infected and damaged cells. In mouse, the recognition of inducible/modif...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1111/j.1600-065X.2006.00481.x

    authors: Jabri B,Ebert E

    更新日期:2007-02-01 00:00:00

  • The role of the integrin LFA-1 in T-lymphocyte migration.

    abstract::A successful immune response depends on the migration of lymphocytes into lymph nodes or inflamed tissues where they make contact with antigen-presenting cells. We are interested in how one member of the integrin family, leukocyte function-associated antigen-1 (LFA-1), controls the function and, in particular, the mig...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1111/j.1600-065X.2007.00537.x

    authors: Smith A,Stanley P,Jones K,Svensson L,McDowall A,Hogg N

    更新日期:2007-08-01 00:00:00

  • Fine tuning the immune response through B7-H3 and B7-H4.

    abstract:SUMMARY:B7-H3 and B7-H4 belong to a new class of immune regulatory molecules, which primarily execute their functions in peripheral tissues to fine tune immune responses in target organs. In normal circumstances, while the mRNA for both molecules is broadly distributed, tight control at the post-transcriptional level i...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1111/j.1600-065X.2009.00768.x

    authors: Yi KH,Chen L

    更新日期:2009-05-01 00:00:00

  • From HLA-B27 to spondyloarthritis: a journey through the ER.

    abstract::Almost four decades of research into the role of human leukocyte antigen-B27 (HLA-B27) in susceptibility to spondyloarthritis has yet to yield a convincing answer. New results from an HLA-B27 transgenic rat model now demonstrate quite convincingly that CD8(+) T cells are not required for the inflammatory phenotype. Di...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1111/j.0105-2896.2009.00865.x

    authors: Colbert RA,DeLay ML,Klenk EI,Layh-Schmitt G

    更新日期:2010-01-01 00:00:00

  • Establishment and functional implications of B-cell connectivity.

    abstract::We have discussed some aspects of the structure of the normal immune system, particularly the B-cell compartment. We have argued: that a basic property of the natural antibody repertoire is constituted by high degrees of connectivity within the immune system as well as between the system and other components of the or...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1111/j.1600-065x.1989.tb00028.x

    authors: Holmberg D,Andersson A,Carlsson L,Forsgren S

    更新日期:1989-08-01 00:00:00

  • Established and emergent roles for Ikaros transcription factors in lymphoid cell development and function.

    abstract::Ikaros zinc finger transcription factors are important regulators of the gene programs underlying the development of hematopoietic cell lineages. The family consists of five members: Ikaros, Helios, Aiolos, Eos, and Pegasus, which engage in both homo- and heterotypic intrafamilial interactions to exert diverse functio...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1111/imr.12936

    authors: Read KA,Jones DM,Freud AG,Oestreich KJ

    更新日期:2020-12-17 00:00:00

  • Polyvalent vaccine approaches to combat HIV-1 diversity.

    abstract::A key unresolved challenge for developing an effective HIV-1 vaccine is the discovery of strategies to elicit immune responses that are able to cross-protect against a significant fraction of the diverse viruses that are circulating worldwide. Here, we summarize some of the immunological implications of HIV-1 diversit...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1111/imr.12516

    authors: Korber B,Hraber P,Wagh K,Hahn BH

    更新日期:2017-01-01 00:00:00

  • The roles of Dok family adapters in immunoreceptor signaling.

    abstract::The mammalian Dok protein family has seven members (Dok-1-Dok-7). The Dok proteins share structural similarities characterized by the NH2-terminal pleckstrin homology and phosphotyrosine-binding domains followed by SH2 target motifs in the COOH-terminal moiety, indicating an adapter function. Indeed, Dok-1 was origina...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1111/j.1600-065X.2009.00844.x

    authors: Mashima R,Hishida Y,Tezuka T,Yamanashi Y

    更新日期:2009-11-01 00:00:00

  • Genesis of the ILT/LIR/MIR clusters within the human leukocyte receptor complex.

    abstract::The human leukocyte receptor complex (LRC) contains at least 26 genes which belong to the immunoglobulin superfamily The genes include two clusters of immunoglobulin-like transcript (ILT)/leukocyte immunoglobulin-like receptor (LIR)/monocyte-macrophage inhibitory receptor (MIR) loci, a cluster of killer cell inhibitor...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1034/j.1600-065x.2001.1810103.x

    authors: Volz A,Wende H,Laun K,Ziegler A

    更新日期:2001-06-01 00:00:00

  • Preclinical evaluation of human hematolymphoid function in the SCID-hu mouse.

    abstract::Work in the SCID-hu system has progressed significantly over the past 3-4 years. Reliable SCID-hu constructs can now be created for the evaluation of long-term multilineage human hematopoiesis, human immune function, and HIV infection of human hematolymphoid organs in vivo. Given these constructs, a variety of therape...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1111/j.1600-065x.1991.tb00615.x

    authors: McCune JM,Péault B,Streeter PR,Rabin L

    更新日期:1991-12-01 00:00:00

  • The role of innate immunity in Alzheimer's disease.

    abstract::The amyloid hypothesis has dominated Alzheimer's disease (AD) research for almost 30 years. This hypothesis hinges on the predominant clinical role of the amyloid beta (Aβ) peptide in propagating neurofibrillary tangles (NFTs) and eventual cognitive impairment in AD. Recent research in the AD field has identified the ...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1111/imr.12896

    authors: Ennerfelt HE,Lukens JR

    更新日期:2020-09-01 00:00:00

  • Immune memory redefined: characterizing the longevity of natural killer cells.

    abstract::Natural killer (NK) cells respond rapidly to transformed, stressed, or virally infected cells and provide a first-line immune defense against pathogen invasion and cancer. Thought to involve short-lived effector cells that are armed for battle, NK cells were not previously known to contribute in recall responses to pa...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1111/j.1600-065X.2010.00900.x

    authors: Sun JC,Beilke JN,Lanier LL

    更新日期:2010-07-01 00:00:00

  • The grateful dead: damage-associated molecular pattern molecules and reduction/oxidation regulate immunity.

    abstract::The response to pathogens and damage in plants and animals involves a series of carefully orchestrated, highly evolved, molecular mechanisms resulting in pathogen resistance and wound healing. In metazoans, damage- or pathogen-associated molecular pattern molecules (DAMPs, PAMPs) execute precise intracellular tasks an...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1111/j.1600-065X.2007.00579.x

    authors: Lotze MT,Zeh HJ,Rubartelli A,Sparvero LJ,Amoscato AA,Washburn NR,Devera ME,Liang X,Tör M,Billiar T

    更新日期:2007-12-01 00:00:00

  • Cell biology and immunology of Leishmania.

    abstract::More than 20 years ago, immunologists discovered that resistance and susceptibility to experimental infection with the intracellular protozoan Leishmania major was associated with the development of T-helper 1 (Th1)- and Th2-dominated immune responses, respectively. This infectious disease model was later used to iden...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1111/j.1600-065X.2010.00983.x

    authors: Mougneau E,Bihl F,Glaichenhaus N

    更新日期:2011-03-01 00:00:00

  • The functional network of ion channels in T lymphocytes.

    abstract::For more than 25 years, it has been widely appreciated that Ca2+ influx is essential to trigger T-lymphocyte activation. Patch clamp analysis, molecular identification, and functional studies using blockers and genetic manipulation have shown that a unique contingent of ion channels orchestrates the initiation, intens...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1111/j.1600-065X.2009.00816.x

    authors: Cahalan MD,Chandy KG

    更新日期:2009-09-01 00:00:00

  • Development, trafficking, and function of memory T-cell subsets.

    abstract::The precise mechanisms that govern memory T-cell lineage commitment during an immune response continue to be the subject of intense scrutiny. The existence of memory T-cell subsets defined by location, function, and phenotype adds an additional layer of complexity to the overall memory T-cell population. In this revie...

    journal_title:Immunological reviews

    pub_type: 杂志文章,评审

    doi:10.1111/j.0105-2896.2006.00393.x

    authors: Lefrançois L

    更新日期:2006-06-01 00:00:00