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Originally published In Press as doi:10.1074/mcp.M600310-MCP200 on October 29, 2006.
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Molecular & Cellular Proteomics 6:102-113, 2007.
© 2007 by The American Society for Biochemistry and Molecular Biology, Inc.

Research

Distorted Relation between mRNA Copy Number and Corresponding Major Histocompatibility Complex Ligand Density on the Cell Surface*,S

Andreas O. Weinzierl{ddagger}, Claudia Lemmel{ddagger}, Oliver Schoor{ddagger}, Margret Müller{ddagger}, Tobias Krüger{ddagger}, Dorothee Wernet§, Jörg Hennenlotter, Arnulf Stenzl, Karin Klingel||, Hans-Georg Rammensee{ddagger} and Stefan Stevanovic{ddagger},**,{ddagger}{ddagger}

From the {ddagger} Department of Immunology, Institute for Cell Biology, University of Tübingen and ** Proteome Centrum Tübingen, Auf der Morgenstelle 15, 72076 Tübingen, Germany, § Institute of Clinical and Experimental Transfusion Medicine, University of Tübingen, Otfried-Müller-Str. 4/1, 72076 Tübingen, Germany, Department of Urology, University of Tübingen, Hoppe-Seyler-Strasse 3, 72076 Tübingen, Germany, and || Department of Molecular Pathology, Universtiy of Tübingen, Liebermeisterstrasse 8, 72076 Tübingen, Germany

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. Because such dependences are of intrinsic importance for the detailed understanding of translation efficiency and protein turnover and thus for systems biology in general and for tumor immunotherapy in practical application, we quantitatively analyzed 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 renal cell carcinoma. A significant number of peptides presented predominantly on tumor or normal tissue showed no or only minor changes in mRNA expression levels. In several cases, peptides could even be identified despite the virtual absence of the respective mRNA. Thus we conclude that a majority of epitopes from tumor-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.

{ddagger}{ddagger} To whom correspondence should be addressed. Tel.: 49-7071-2987645; Fax: 49-7071-295653; E-mail: stefan.stevanovic{at}uni-tuebingen.de


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