| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on August 14, 2006
Department of Immunology, Institute of Cell Biology, University of Tuebingen, Tuebingen 72076
Corresponding Author: andreas.weinzierl{at}uni-tuebingen.de
The major histocompatibility complex (MHC) presents peptides derived from degraded cellular proteins to T-cells and is thus crucial for triggering specific immune responses against viral infections or cancer. Up to now, there has been no evidence for a correlation between levels of mRNA (the “transcriptome”) and the density of MHC:peptide complexes (the “MHC ligandome”) on cells. Since such dependencies are of intrinsic importance for the detailed understanding of translation efficiency and protein turnover, and thus for systems biology in general and for tumour immunotherapy in practical application, we quantitatively analysed the levels of mRNA and corresponding MHC ligand densities in samples of renal cell carcinomas and their autologous normal kidney tissues. Relative quantification was carried out by gene chip analysis and by stable isotope peptide labeling, respectively. In comparing more than 270 pairs of gene expression and corresponding peptide presentation ratios, we demonstrate that there is no clear correlation (R = 0.32) between mRNA levels and corresponding MHC peptide levels in RCC. A significant number of peptides presented predominantly on tumour or normal tissue showed no or only minor changes in mRNA expression levels. In several cases, peptides could even be identified in spite of the virtual absence of the respective mRNA. Thus we conclude that a majority of epitopes from tumour associated antigens will not be found in approaches based mainly on mRNA expression studies, as mRNA expression reflects a distorted picture of the situation on the cell surface as visible for T cells.
Revised on October 11, 2006
Accepted on October 30, 2006
Distorted relation between mRNA copy number and corresponding major histocompatibility complex ligand density on the cell surface
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  V. S. Meyer, W. Kastenmuller, G. Gasteiger, M. Franz-Wachtel, T. Lamkemeyer, H.-G. Rammensee, S. Stevanovic, D. Sigurdardottir, and I. Drexler Long-Term Immunity against Actual Poxviral HLA Ligands as Identified by Differential Stable Isotope Labeling J. Immunol., November 1, 2008; 181(9): 6371 - 6383. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. O. Weinzierl, D. Maurer, F. Altenberend, N. Schneiderhan-Marra, K. Klingel, O. Schoor, D. Wernet, T. Joos, H.-G. Rammensee, and S. Stevanovic A Cryptic Vascular Endothelial Growth Factor T-Cell Epitope: Identification and Characterization by Mass Spectrometry and T-Cell Assays Cancer Res., April 1, 2008; 68(7): 2447 - 2454. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.-H. Fortier, E. Caron, M.-P. Hardy, G. Voisin, S. Lemieux, C. Perreault, and P. Thibault The MHC class I peptide repertoire is molded by the transcriptome J. Exp. Med., March 17, 2008; 205(3): 595 - 610. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Yewdell and H. D. Hickman New lane in the information highway: alternative reading frame peptides elicit T cells with potent antiretrovirus activity J. Exp. Med., October 29, 2007; 204(11): 2501 - 2504. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| All ASBMB Journals | Journal of Biological Chemistry |
| Journal of Lipid Research | ASBMB Today |
