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Identification of a biological ligand for human plasmacytid dendritic cell receptor ILT7
Author(s) -
Cao Wei,
Bover Laura,
Wang YiHong,
Rosen David B,
Arai Naoko,
Yao Zhengbin,
Lanier Lewis L,
Liu YongJun
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1065.17
Subject(s) - biology , monoclonal antibody , microbiology and biotechnology , crosstalk , cancer cell , haematopoiesis , tumor microenvironment , receptor , ligand (biochemistry) , cell culture , cancer research , antibody , immune system , cancer , immunology , stem cell , genetics , physics , optics
Human plasmacytoid dendritic cells (pDCs) are instrumental for systemic type I IFN production during viral infections. How these cells crosstalk with other cell types during steady state and/or after the initial IFN burst is not clear. Using a reporter cell system, we discovered that a list of breast cancer cell lines were potent in triggering human pDC specific receptor ILT7, indicating the presence of a potential biological ligand on these cells. Monoclonal antibodies were generated against ILT7 ligand positive cancer cells and two clones were able to neutralize the abilities of cancer cells to activate ILT7. Using these mAbs, we found that, in addition to transformed cells, normal peripheral hematopoietic and non‐hematopoietic cells up‐regulate the expression of such molecule in response to IFN exposure. We have screened a cDNA library using the mAbs and identified a putative candidate gene. Confirmation is underway to establish the role of this molecule as the ligand for ILT7. As ILT7 activates a potent ITAM‐mediated negative regulatory pathway in pDCs, our findings may suggest a converged molecular mechanism modulating pDC function, which may operate in a tumor microenvironment or in a negative feedback manner post IFN production.