Please note that eDoc will be permanently shut down in the first quarter of 2021!      Home News About Us Contact Contributors Disclaimer Privacy Policy Help FAQ

Home
Search
Quick Search
Advanced
Fulltext
Browse
Collections
Persons
My eDoc
Session History
Login
Name:
Password:
Documentation
Help
Support Wiki
Direct access to
document ID:


          Institute: MPI für Biochemie     Collection: Structural Biology (W. Baumeister)     Display Documents



  history
ID: 318589.0, MPI für Biochemie / Structural Biology (W. Baumeister)
Expression and function of the peptide transporters in escape variants of human renal cell carcinomas
Authors:Seliger, B.; Hohne, A.; Jung, D.; Kallfelz, M.; Knuth, A.; Jaeger, E.; Bernhard, H.; Momburg, F.; Tampe, R.; Huber, C.
Date of Publication (YYYY-MM-DD):1997-07
Title of Journal:Experimental Hematology
Volume:25
Issue / Number:7
Start Page:608
End Page:614
Review Status:not specified
Audience:Not Specified
Abstract / Description: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. [References: 46]
Free Keywords:Renal cell carcinoma; Malignant transformation; Antigen presentation; Transporters; Mhc class i antigens.; Major histocompatibility complex; Class-i molecules; T-lymphocytes; Encoded transporter; Down-regulation; Hla expression; Ifn-gamma; Mhc; Region.; Cardiovascular & hematology research.
External Publication Status:published
Document Type:Article
Communicated by:Anton Hillebrand
Affiliations:MPI für Biochemie/Structural Biology (W. Baumeister)
The scope and number of records on eDoc is subject to the collection policies defined by each institute - see "info" button in the collection browse view.