CD1 Recognition by Mouse NK1
            <sup>+</sup>
            T Lymphocytes

Bendelac, Albert; Lantz, Olivier; Quimby, Mary E.; Yewdell, Jonathan W.; Bennink, Jack R.; Brutkiewicz, Randy R.

doi:10.1126/science.7538697

Cited by 841 publications

(646 citation statements)

References 37 publications

Supporting

Mentioning

625

Contrasting

Unclassified

Order By: Relevance

“…The Va14 hybridomas gave only moderate responses to splenocytes, and no, or very low, responses to syngeneic thymocytes or the tested CD1d-transfectants. This is somewhat in contrast to results obtained by others [2], but it should be noted that the hybridomas presented here were selected only by the type of TCR, not by their reactivity, thus auto-or direct CD1d-reactivity may not be a feature of all Va14 NKT cells.…”

Section: Discussioncontrasting

confidence: 87%

“…Natural killer (NK) T cells (NKT) represent a unique subset, which differs from the conventional T cells by the expression of activation markers and markers characteristic for NK cells (NK1.1, CD122, CD16 and members of the Ly49 family) [1], and reactivity to the major histocompatibility complex (MHC) class I-like molecule CD1 [2]. The cells are present at low percentage in most lymphoid organs, i.e.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Differences in the Ligand Specificity between CD1d‐Restricted T Cells with Limited and Diverse T‐Cell Receptor Repertoire

et al. 2000

View full text Add to dashboard Cite

The natural killer (NK) T-lymphocyte population consists of two subsets utilizing a diverse and restricted Tcell receptor (TCR) repertoire, respectively. Both populations have been shown to include autoreactive cells. NKT cells carrying restricted Va14(AV14S1)Ja281/Vb8.2(BV8S2A1) TCR have been shown to recognize a-galactosylceramide (aGalCer) presented in the context of murine CD1d. In this study we screened a set of murine CD1d-autoreactive T-cell hybridomas with diverse TCR for their reactivity with several glycosylated variants of ceramide, including aGalCer. These hybridomas showed a different pattern of reactivity to CD1d-expressing antigen-presenting cells (APC) and were not reactive with any of the tested variants of ceramide. A second set of hybridomas had been selected for expression of Va14 and Vb8.2 TCR chains. These cells responded to aGalCer presented on CD1d, but were only weakly reactive to syngeneic splenocytes or CD1d-transfected cells. Their ®ne speci®city in the response to glycosylation variants of ceramide demonstrated a homogenous reactivity pattern, including reactivity to a-galactosylsphingosine, the variant of aGalCer with truncated fatty acyl chain. These ®ndings underline the differences in ligand speci®city between the two subsets of CD1d-restricted NKT cells, and demonstrate a similarity in reactivity among the hybridomas using the Va14-Ja281/Vb8.2 TCR.

show abstract

Section: Discussioncontrasting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Differences in the Ligand Specificity between CD1d‐Restricted T Cells with Limited and Diverse T‐Cell Receptor Repertoire

et al. 2000

View full text Add to dashboard Cite

show abstract

“…DN32.D3 cells, a murine NKT cell hybridoma cell line (42), provided by Dr. A. Bendelac (Princeton University, Princeton, NJ), were cultured in DMEM supplemented with 5% FBS, 100 U/ml penicillin, and 100 mg/ml streptomycin.…”

Section: Cell Lines and Culture Mediamentioning

confidence: 99%

The Bile Acid Sensor Farnesoid X Receptor Is a Modulator of Liver Immunity in a Rodent Model of Acute Hepatitis

Mencarelli

Renga²,

Migliorati³

et al. 2009

The Journal of Immunology

144

110

View full text Add to dashboard Cite

Immune-mediated liver diseases including autoimmune and viral hepatitis are a major health problem worldwide. In this study, we report that activation of the farnesoid X receptor (FXR), a member of the ligand-activated nuclear receptor superfamily and bile sensor highly expressed in the liver, attenuates liver injury in a model of autoimmune hepatitis induced by Con A. We found that FXR gene ablation results in a time-dependent increase of liver expression (up to 20-fold in a 9-mo-old mouse) of osteopontin, a NKT cell-derived extracellular matrix protein and immunoregulatory cytokine. In comparison to wild-type, FXR−/− mice are more susceptible to Con A-induced hepatitis and react to Con A administration by an unregulated production of osteopontin. Administering wild-type mice with a synthetic FXR agonist attenuated Con A-induced liver damage and liver expression of the osteopontin gene. By in vitro studies, we found that FXR is expressed by primarily isolated NKT cells and its ablation favors ostepontin production in response to Con A. Chromatin immunoprecipitation assay and coimmunoprecipitation experiments demonstrate that the short heterodimer partner (SHP), a nuclear receptor and FXR target, was expressed by NKT cell hybridomas and increased in response to FXR activation. FXR activates SHP that interacts with and inhibits c-Jun binding to the osteopontin promoter. These data indicate that in NKT cells, FXR activation causes a SHP-mediated inhibition of osteopontin production. These data support the notion that the bile acid sensor FXR regulates the activation of liver NKT cells.

show abstract

“…TCR from both species recognizes CD1d (18,19), a member of the CD1 family of Ag-presenting molecules that is so conserved between humans and mice that in vitro human and mouse inv. NKT cell clones recognize APC expressing either mouse or human CD1d, respectively (20).…”

Section: N Atural Killer T Cells Are T Lymphocytes That Coexpress Thementioning

confidence: 99%

Human Invariant Vα24-JαQ TCR Supports the Development of CD1d-Dependent NK1.1+ and NK1.1− T Cells in Transgenic Mice

Capone

Cantarella

Schumann

et al. 2003

The Journal of Immunology

View full text Add to dashboard Cite

A sizable fraction of T cells expressing the NK cell marker NK1.1 (NKT cells) bear a very conserved TCR, characterized by homologous invariant (inv.) TCR Vα24-JαQ and Vα14-Jα18 rearrangements in humans and mice, respectively, and are thus defined as inv. NKT cells. Because human inv. NKT cells recognize mouse CD1d in vitro, we wondered whether a human inv. Vα24 TCR could be selected in vivo by mouse ligands presented by CD1d, thereby supporting the development of inv. NKT cells in mice. Therefore, we generated transgenic (Tg) mice expressing the human inv. Vα24-JαQ TCR chain in all T cells. The expression of the human inv. Vα24 TCR in TCR Cα−/− mice indeed rescues the development of inv. NKT cells, which home preferentially to the liver and respond to the CD1d-restricted ligand α-galactosylceramide (α-GalCer). However, unlike inv. NKT cells from non-Tg mice, the majority of NKT cells in Vα24 Tg mice display a double-negative phenotype, as well as a significant increase in TCR Vβ7 and a corresponding decrease in TCR Vβ8.2 use. Despite the forced expression of the human CD1d-restricted TCR in Cα−/− mice, staining with mCD1d-α-GalCer tetramers reveals that the absolute numbers of peripheral CD1d-dependent T lymphocytes increase at most by 2-fold. This increase is accounted for mainly by an increased fraction of NK1.1− T cells that bind CD1d-α-GalCer tetramers. These findings indicate that human inv. Vα24 TCR supports the development of CD1d-dependent lymphocytes in mice, and argue for a tight homeostatic control on the total number of inv. NKT cells. Thus, human inv. Vα24 TCR-expressing mice are a valuable model to study different aspects of the inv. NKT cell subset.

show abstract

CD1 Recognition by Mouse NK1 ⁺ T Lymphocytes

Cited by 841 publications

References 37 publications

Differences in the Ligand Specificity between CD1d‐Restricted T Cells with Limited and Diverse T‐Cell Receptor Repertoire

Differences in the Ligand Specificity between CD1d‐Restricted T Cells with Limited and Diverse T‐Cell Receptor Repertoire

The Bile Acid Sensor Farnesoid X Receptor Is a Modulator of Liver Immunity in a Rodent Model of Acute Hepatitis

Human Invariant Vα24-JαQ TCR Supports the Development of CD1d-Dependent NK1.1+ and NK1.1− T Cells in Transgenic Mice

Contact Info

Product

Resources

About

CD1 Recognition by Mouse NK1 + T Lymphocytes

Cited by 841 publications

References 37 publications

Differences in the Ligand Specificity between CD1d‐Restricted T Cells with Limited and Diverse T‐Cell Receptor Repertoire

Differences in the Ligand Specificity between CD1d‐Restricted T Cells with Limited and Diverse T‐Cell Receptor Repertoire

The Bile Acid Sensor Farnesoid X Receptor Is a Modulator of Liver Immunity in a Rodent Model of Acute Hepatitis

Human Invariant Vα24-JαQ TCR Supports the Development of CD1d-Dependent NK1.1+ and NK1.1− T Cells in Transgenic Mice

Contact Info

Product

Resources

About

CD1 Recognition by Mouse NK1 ⁺ T Lymphocytes