Abstract
The major histocompatibility complex (MHC) peptide repertoire of cancer cells serves both as a source for new tumor antigens for development of cancer immunotherapy and as a rich information resource about the protein content of the cancer cells (their proteome). Thousands of different MHC peptides are normally displayed by each cell, where most of them are derived from different proteins and thus represent most of the cellular proteome. However, in contrast to standard proteomics, which surveys the cellular protein contents, analyses of the MHC peptide repertoire correspond more to the rapidly degrading proteins in the cells (i.e. the transient proteome). MHC peptides can be efficiently purified by affinity chromatography from membranal MHC molecules, or preferably following transfection of vectors for expression of recombinant soluble MHC molecules. The purified peptides are resolved and analyzed by capillary high-pressure liquid chromatography-electrospray ionization-tandem mass spectrometry, and the data are deciphered with new software tools enabling the creation of large databanks of MHC peptides displayed by different cell types and by different MHC haplotypes. These lists of identified MHC peptides can now be used for searching new tumor antigens, and for identification of proteins whose rapid degradation is significant to cancer progression and metastasis. These lists can also be used for identification of new proteins of yet unknown function that are not detected by standard proteomics approaches. This review focuses on the presentation, identification and analysis of MHC peptides significant for cancer immunotherapy. It is also concerned with the aspects of human proteomics observed through large-scale analyses of MHC peptides.
Footnotes
-
Published, MCP Papers in Press, June 23, 2003, DOI 10.1074/mcp.R300004-MCP200
-
↵1 The abbreviations used are: MHC, major histocompatibility complex; sMHC, soluble major histocompatibility complex; HLA, human leukocytes antigen; TCR, T cell receptor; TSA, tumor-specific antigens; TAA, tumor-associated antigens; SEREX, serological identification of antigens by recombinant expression cloning; ER, endoplasmic reticulum; LC, liquid chromatography; MS, mass spectrometry; MS/MS, tandem mass spectrometry; ORF, open reading frame.
-
↵2 Beer, I., Barnea, E., Ziv, T., and Admon, A., submitted for publication.
-
↵* This work was supported by The Greta Koppel Small Cell Lung Cancer Fund and by the Smoler Proteomics Center at the Technion and by the Israel Ministry of Science. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
- Received May 15, 2003.
- Revision received June 23, 2003.
- © 2003 The American Society for Biochemistry and Molecular Biology