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Document Version Version Comment Date Status
318589.0 [No comment] 07.08.2012 13:27 Released

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
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)