Linked Life Data

18087220

Source:http://linkedlifedata.com/resource/pubmed/id/18087220

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2008-4-28
pubmed:abstractText
Dendritic cells (DC) operate through an immature (iDC) step (where tumor antigens are internalized) and a mature step (mDC) (where tumor antigens (TA) are cross-presented to naive TA-specific cytotoxic T lymphocyte (CTL) progenitors). Receptors by which cellbound antigens can access the DC cross-presentation pathway include the Fcgamma receptors (FcgammaR). This route has been exploited to deliver opsonized tumors to DC and promising results have been obtained with mAbs raised against overexpressed or specific tumor antigens. In order to extend this strategy to tumor for which no antigens have been described, we have exploited the ubiquitous molecule MHC Class I as target antigen. The low membrane expression of tumor antigens on KATO cells, a previously studied human gastric carcinoma cell line, suggested its use here as a model. The IgG1 TP25.99 and the IgG2a W6/32 anti-MHC Class I mAbs, which strongly reacted with KATO cells, where employed as tumor coating mAbs. Since these mAbs recognize the FcgammaRI (CD64) and FcgammaRIII (CD16), respectively on DCs, the frequencies of the two classes of FcgammaRI on DCs was evaluated. CD64 was expressed on 35% of iDCs compared to 11% expression of CD16, the two molecules being co-expressed. IgG1 mAb-opsonized KATO (KATO(TP25)) cells were taken up by iDCs with the same efficiency as KATO cells opsonized with IgG2a mAb (KATO(W6/32)), but induced a higher expression of the maturation marker CD83. CTL cross-priming by KATO(TP25) (but not KATO(W6/32))-loaded and cytokine-matured DCs was also higher than cross-priming induced by uncoated- or FcgammaRI-targeted KATO(W6/32)-DC. Together the present results indicate that: (i) MHC Class I antigens are advantageous antigens for targeting tumor cells to the FcgammaR-mediated cross-presentation pathway and (ii) immunogenic signals seem to be prevalently conveyed by FcgammaRIII.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1555-8576
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
6
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1932-7
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:18087220-Animals, pubmed-meshheading:18087220-Antibodies, Monoclonal, pubmed-meshheading:18087220-Antibody Specificity, pubmed-meshheading:18087220-Antigen Presentation, pubmed-meshheading:18087220-Antigens, Neoplasm, pubmed-meshheading:18087220-Carcinoma, pubmed-meshheading:18087220-Cell Differentiation, pubmed-meshheading:18087220-Cell Line, Tumor, pubmed-meshheading:18087220-Coculture Techniques, pubmed-meshheading:18087220-Cytokines, pubmed-meshheading:18087220-Dendritic Cells, pubmed-meshheading:18087220-GPI-Linked Proteins, pubmed-meshheading:18087220-HLA-A2 Antigen, pubmed-meshheading:18087220-Humans, pubmed-meshheading:18087220-Interferon-gamma, pubmed-meshheading:18087220-K562 Cells, pubmed-meshheading:18087220-Mice, pubmed-meshheading:18087220-Opsonin Proteins, pubmed-meshheading:18087220-Receptors, IgG, pubmed-meshheading:18087220-Stomach Neoplasms, pubmed-meshheading:18087220-T-Lymphocytes, Cytotoxic
pubmed:year
2007
pubmed:articleTitle
Contribution of dendritic cells' FcgammaRI and FcgammaRIII to cross-presentation of tumor cells opsonized with the anti-MHC class I monoclonal antibodies.
pubmed:affiliation
Laboratory of Tumor Immunology, University of Turin, Turin, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't