RGD Reference Report - Cross-linking a mAb to NKR-P2/NKG2D on dendritic cells induces their activation and maturation leading to enhanced anti-tumor immune response. - Rat Genome Database

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Cross-linking a mAb to NKR-P2/NKG2D on dendritic cells induces their activation and maturation leading to enhanced anti-tumor immune response.

Authors: Srivastava, RM  Varalakshmi, CH  Khar, A 
Citation: Srivastava RM, etal., Int Immunol. 2007 May;19(5):591-607. Epub 2007 Mar 15.
RGD ID: 9685185
Pubmed: PMID:17369187   (View Abstract at PubMed)
DOI: DOI:10.1093/intimm/dxm024   (Journal Full-text)

NKR-P2/NKG2D is the chief tumor recognition receptor of NK cells and some T cells, which recognizes stress inducible ligands on tumors and mediates cell activation. We have recently reported the involvement of NKR-P2 in rat dendritic cell (DC) activation. We demonstrate the potential of agonistic anti-NKR-P2 mAb (1A6), which mimics the NKR-P2 ligand and induces activation and maturation of DCs. Interaction of DCs with 1A6 enhances nitric oxide-mediated apoptosis in tumor cells. Cross-linking of NKR-P2 with mAb1A6 up-regulates MHC II, CD86, CD1a, antigen-presentation function and decreases endocytic activity of DC, thus drives DCs to play a pivotal role in adaptive immune responses. NKR-P2 cross-linking with 1A6 also induced the secretion of inflammatory cytokines, IL-1beta, tumor necrosis factor-alpha, IFN-gamma and IL-12 by DCs. Blocking of 1A6-mediated activation and maturation with inhibitors of PI3K, p38K and ERK1/2K suggests involvement of MAP kinase in signal transduction. 1A6 cross-linking activates nuclear factor kappa B, which acts as key executioner of DC activation. Administration of 1A6 antibody induces rapid regression and protective immune responses against transplantable tumors, suggesting mAb induced activation and maturation of DCs, leading to enhanced anti-tumor immune response.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Klrk1Ratpositive regulation of myeloid dendritic cell activation  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Klrk1  (killer cell lectin like receptor K1)


Additional Information