β2-Microglobulin deficient mice lack CD4−8+ cytolytic T cells

Zijlstra, Maarten; Bix, Mark; Simister, Neil E.; Loring, Janet; Raulet, David H.; Jaenisch, Rudolf

doi:10.1038/344742a0

Cited by 960 publications

(580 citation statements)

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“…In relation to V2R-mediated chemoreception, Go mutants (Chamero et al, 2011) show reduced intermale and maternal aggression. In addition, Loconto et al (2003) analysed a mouse mutant line knockout for β2-microglobulin (generated by Zijlstra et al, 1990), a protein expressed in vomeronasal neurons where it contributes to escort V2R to the cell surface. Consequently, in these mutants V2R are misallocated and pheromone detection through V2R is expected to be deficient.…”

Section: Role Of the Vomeronasal And Olfactory Epithelia On Aggressionmentioning

confidence: 99%

From sexual attraction to maternal aggression: When pheromones change their behavioural significance

Martín‐Sánchez

McLean

Beynon

et al. 2015

Hormones and Behavior

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From sexual attraction to maternal aggression: When pheromones change their behavioural significance, Hormones and Behavior (2014), doi: 10.1016/j.yhbeh.2014 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT2 AbstractThis paper reviews the role of chemosignals in the socio-sexual interactions of female mice, and reports two experiments testing the role of pup-derived chemosignals and the male sexual pheromone darcin in inducing and promoting maternal aggression. Female mice are attracted to urine-borne male pheromones. Volatile and non-volatile urine fractions have been proposed to contain olfactory and vomeronasal pheromones. In particular, the male-specific major urinary protein (MUP) MUP20, darcin, has been shown to be rewarding and attractive to females. Non-urinary male chemosignals, such as the lacrimal protein ESP1, promote lordosis in female mice, but its attractive properties are still to be tested. There is evidence indicating that ESP1 and MUPs are detected by vomeronasal type 2 receptors (V2R).When a female mouse becomes pregnant, she undergoes dramatic changes in her physiology and behaviour. She builds a nest for her pups and takes care of them. Dams also defend the nest against conspecific intruders, attacking especially gonadally intact males. Maternal behaviour is dependent on a functional olfactory system, thus suggesting a role of chemosignals in the development of maternal behaviour. Our first experiment demonstrates, however, that pup chemosignals are not sufficient to induce maternal aggression in virgin females. In addition, it is known that vomeronasal stimuli are needed for maternal aggression.Since MUPs (and other molecules) are able to promote intermale aggression, in our second experiment we test if the attractive MUP darcin also promotes attacks on castrated male intruders by lactating dams. Our findings demonstrate that the same chemosignal, darcin, promotes attraction or aggression according to female reproductive state.

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Section: Role Of the Vomeronasal And Olfactory Epithelia On Aggressionmentioning

confidence: 99%

From sexual attraction to maternal aggression: When pheromones change their behavioural significance

Martín‐Sánchez

McLean

Beynon

et al. 2015

Hormones and Behavior

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“…Genetic engineering of HLA expression provides a means of generating allogeneic cells and can be targeted directly (e.g., β2-microglobulin (B2M)) or indirectly via transcription factors and transporter pathways. B2M is required for successful surface assembly of MHC class I molecules [94], with B2M knockout resulting in cells devoid of major histocompatibility complex-I (MHC-I) expression [95]. Some groups have endeavored to downregulate the B2M and HLA loci in primary T cells [96, 97].…”

Section: Applicationsmentioning

confidence: 99%

Genome-Edited T Cell Therapies

Delhove

Qasim

2017

Curr Stem Cell Rep

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Purpose of ReviewAlternative approaches to conventional drug-based cancer treatments have seen T cell therapies deployed more widely over the last decade. This is largely due to their ability to target and kill specific cell types based on receptor recognition. Introduction of recombinant T cell receptors (TCRs) using viral vectors and HLA-independent T cell therapies using chimeric antigen receptors (CARs) are discussed. This article reviews the tools used for genome editing, with particular emphasis on the applications of site-specific DNA nuclease mediated editing for T cell therapies.Recent FindingsGenetic engineering of T cells using TCRs and CARs with redirected antigen-targeting specificity has resulted in clinical success of several immunotherapies. In conjunction, the application of genome editing technologies has resulted in the generation of HLA-independent universal T cells for allogeneic transplantation, improved T cell sustainability through knockout of the checkpoint inhibitor, programmed cell death protein-1 (PD-1), and has shown efficacy as an antiviral therapy through direct targeting of viral genomic sequences and entry receptors.SummaryThe combined use of engineered antigen-targeting moieties and innovative genome editing technologies have recently shown success in a small number of clinical trials targeting HIV and hematological malignancies and are now being incorporated into existing strategies for other immunotherapies.

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“…A ganglioside mixture composed of G M3 (Neu5Ac), IV 3 Neu5Ac-nLcOse 4 Cer (IV 3 nLc4), IV 6 Neu5Ac-nLcOse 4 Cer (IV 6 nLc4) and VI 3 Neu5Ac-nLcOse 6 Cer (VI 3 nLc6) was isolated from human granulocytes as previously described [23]. G M3 (Neu5Gc) was purified from a mouse-mouse hybridoma [24].…”

Section: Thin-layer Chromatography and Reference Gangliosidesmentioning

confidence: 99%

“…Rabbit anti-GgOse 4 Cer antiserum used for the detection of G M1b and G D1a has also been described in earlier publications [28,29]. Highly specific chicken anti-GalNAc-G M1b antibody has been described in detail elsewhere [25,26], as well as chicken antinLcOse 4 Cer antibody used for the analysis of neolacto-series gangliosides [27,30,31]. Cholera toxin B subunit (= choleragenoid) specific for ganglioside G M1 was from Sigma (Deisenhofen, Germany) and goat anti-choleragenoid antiserum from Calbiochem (Frankfurt, Germany).…”

Section: Antibodies and Cholera Toxin B Subunit (Choleragenoid)mentioning

confidence: 99%

“…Neuraminidase treatment of neolacto-series gangliosides with (a2-3)-substituted sialic acid is necessary prior to immunostaining with anti-nLcOse 4 Cer antibody, whereas (a2-6)-sialylated neolacto-type gangliosides can be detected without enzyme treatment because sialylation at position 6 of the terminal galactose does not hinder recognition [30]. Fixed silica gel plates were incubated with 2·5 mU/ml Vibrio cholerae neuraminidase (Behring Werke AG, Marburg, Germany) for 2 h at 37°C in the buffer described above, followed by immunostaining with antinLcOse 4 Cer antibody [30].…”

Section: Tlc Immunostaining Of Neolacto-series Gangliosidesmentioning

confidence: 99%

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Ganglioside expression in tissues of mice lackingβ2-microglobulin

Markotić

Marušić

Tomac

et al. 2002

Clinical and Experimental Immunology

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SUMMARYThis study presents a comparative analysis of gangliosides from lymphoid (spleen and thymus) and other (brain, liver, lungs and muscle) tissues of C57BL/6 mice lacking the gene for b 2 -microglobulin (b 2 M), a constitutive component of the MHC class I molecule. Ganglioside fractions in the tissues of mice homozygous (b 2 M-/-) and heterozygous (b 2 M-/+) for the gene deletion were determined by high performance thin-layer chromatography (HPTLC), followed by immunostaining with specific polyclonal antibodies. Ubiquitous gangliosides G M3 (Neu5Ac) and G M3 (Neu5Gc) were the dominant gangliosides in the lungs of the control b 2 M-/+ mice, whereas the homozygous knockout mice had substantially decreased expression of these structures. The lungs of the b 2 M-/-mice also had reduced expression of T-lymphocyte-specific G M1b -type gangliosides (G M1b and GalNAc-G M1b ). b 2 M-deficient mice also had more G M1a and G D1a gangliosides in the liver, and several neolacto-series gangliosides were increased in the brain and lungs. This study provides in vivo evidence that the b 2 M molecule can influence the acquisition of a distinct ganglioside assembly in different mouse organs, implicating its non-immunological functions.

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β2-Microglobulin deficient mice lack CD4−8+ cytolytic T cells

Cited by 960 publications

References 54 publications

From sexual attraction to maternal aggression: When pheromones change their behavioural significance

From sexual attraction to maternal aggression: When pheromones change their behavioural significance

Genome-Edited T Cell Therapies

Ganglioside expression in tissues of mice lackingβ2-microglobulin

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