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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
7
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pubmed:dateCreated |
1997-8-1
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pubmed:abstractText |
The transporter associated with antigen processing (TAP) complex is a heterodimeric transmembrane pump consisting of the TAP-1 and TAP-2 subunits; these subunits translocate peptides from the cytoplasm into the lumen of the endoplasmic reticulum, where they bind nascent major histocompatibility complex (MHC) class I molecules. Loss or reduced expression of the TAP genes results in the synthesis of unstable peptide free MHC class I molecules that are only weakly expressed on the cell surface. In a number of human tumor cell lines, downregulation of MHC class I expression has been found to be associated with reduced or absent TAP expression. To investigate whether alterations in MHC class I expression occur during transformation and subsequent progression and whether MHC class I suppression is caused by impaired TAP function, we analyzed the protein expression of MHC class I heavy and light chain and TAP-1 in three renal cell carcinoma (RCC) cell lines and short-term cultures from corresponding normal kidney tissue. In one case a cell line established from a metastatic lesion was also available. Compared with normal epithelial cells, suppression of TAP-1 and MHC class I molecules was detected in all three primary RCC cells and was even more pronounced in the metastatic cell line. In contrast to normal epithelial cells, MHC class I membrane expression of two RCC lines was enhanced by culture in the presence of MHC class I binding peptides or at low temperature (26 degrees C) instead of 37 degrees C. Unstable MHC class I surface expression is caused by dissociation of the MHC class I heavy and light chain molecules as a result of functional defects in the antigen processing machinery, e.g., impaired peptide transport. Attempts to counteract the reduced immunogenicity by transferring the TAP genes into these cells demonstrated that TAP-1-modified RCC cells expressed higher levels of MHC class I molecules. These data indicate that downregulation and instability of MHC class I surface expression in RCC cells is at least partially caused by deficient loading with endogenous peptides and can be restored by TAP gene transfer.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/ATP-Binding Cassette Transporters,
http://linkedlifedata.com/resource/pubmed/chemical/Histocompatibility Antigens Class I,
http://linkedlifedata.com/resource/pubmed/chemical/Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/TAP1 protein, human
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0301-472X
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
25
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
608-14
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:9216736-ATP-Binding Cassette Transporters,
pubmed-meshheading:9216736-Biological Transport,
pubmed-meshheading:9216736-Carcinoma, Renal Cell,
pubmed-meshheading:9216736-Cold Temperature,
pubmed-meshheading:9216736-Gene Transfer Techniques,
pubmed-meshheading:9216736-Histocompatibility Antigens Class I,
pubmed-meshheading:9216736-Humans,
pubmed-meshheading:9216736-Kidney Neoplasms,
pubmed-meshheading:9216736-Neoplasm Metastasis,
pubmed-meshheading:9216736-Peptides,
pubmed-meshheading:9216736-Tumor Cells, Cultured
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pubmed:year |
1997
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pubmed:articleTitle |
Expression and function of the peptide transporters in escape variants of human renal cell carcinomas.
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pubmed:affiliation |
Johannes Gutenberg-Universität, Abteilung für Hämatologie/Onkologie, Mainz, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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