About InVivoMAb anti-mouse Jagged 2
The HMJ2-1 monoclonal antibody reacts with mouse Jagged 2 one of many Notch ligands. Jagged 2 is expressed by thymic lymphoid and stromal cells, as well as macrophages and dendritic cells in the spleen. The Notch pathway is an important intercellular signaling pathway that plays a major role in controlling cell fate. The HMJ2-1 antibody has been shown to neutralize Jagged 2 in vivo.
InVivoMAb anti-mouse Jagged 2 Specifications
|Isotype||Armenian Hamster IgG|
|Recommended Isotype Control(s)|
|Recommended Dilution Buffer|
|Immunogen||CHO cells expressing mouse Jagged-2|
in vivo Jagged 2 neutralization
|Sterility||0.2 μM filtered|
|Production||Purified from tissue culture supernatant in an animal free facility|
|Molecular Weight||150 kDa|
|Storage||The antibody solution should be stored at the stock concentration at 4°C. Do not freeze.|
InVivoMAb anti-mouse Jagged (Clone: HMJ2-1)
Riella, L. V., et al. (2013). “Jagged2-signaling promotes IL-6-dependent transplant rejection.” Eur J Immunol 43(6): 1449-1458. PubMed
The Notch pathway is an important intercellular signaling pathway that plays a major role in controlling cell fate. Accumulating evidence indicates that Notch and its ligands present on antigen-presenting cells might be important mediators of T helper cell differentiation. In this study, we investigated the role of Jagged2 in murine cardiac transplantation by using a signaling Jagged2 mAb (Jag2) that activates recombinant signal-binding protein-Jkappa. While administration of Jag2 mAb had little effect on graft survival in the fully allogeneic mismatched model BALB/c–>B6, it hastened rejection in CD28-deficient recipients. Similarly, Jag2 precipitated rejection in the bm12–>B6 model. In this MHC class II-mismatched model, allografts spontaneously survive for >56 days due to the emergence of Treg cells that inhibit the expansion of alloreactive T cells. The accelerated rejection was associated with upregulation of Th2 cytokines and proinflammatory cytokine IL-6, despite expansion of Treg cells. Incubation of Treg cells with recombinant IL-6 abrogated their inhibitory effects in vitro. Furthermore, neutralization of IL-6 in vivo protected Jag2-treated recipients from rejection and Jagged2 signaling was unable to further accelerate rejection in the absence of Treg cells. Our findings therefore suggest that Jagged2 signaling can affect graft acceptance by upregulation of IL-6 and consequent resistance to Treg-cell suppression.
Elyaman, W., et al. (2012). “Notch receptors and Smad3 signaling cooperate in the induction of interleukin-9-producing T cells.” Immunity 36(4): 623-634. PubMed
Interleukin 9 (IL-9) is a pleiotropic cytokine that can regulate autoimmune responses by enhancing regulatory CD4(+)FoxP3(+) T regulatory (Treg) cell survival and T helper 17 (Th17) cell proliferation. Here, we analyzed the costimulatory requirements for the induction of Th9 cells, and demonstrated that Notch pathway cooperated with TGF-beta signaling to induce IL-9. Conditional ablation of Notch1 and Notch2 receptors inhibited the development of Th9 cells. Notch1 intracellular domain (NICD1) recruited Smad3, downstream of TGF-beta cytokine signaling, and together with recombining binding protein (RBP)-Jkappa bound the Il9 promoter and induced its transactivation. In experimental autoimmune encephalomyelitis (EAE), Jagged2 ligation regulated clinical disease in an IL-9-dependent fashion. Signaling through Jagged2 expanded Treg cells and suppressed EAE when administered before antigen immunization, but worsened EAE when administered concurrently with immunization by favoring Th17 cell expansion. We propose that Notch and Smad3 cooperate to induce IL-9 and participate in regulating the immune response.