Tumor antigens and proteomics from the point of view of the major histocompatibility complex peptides.
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.
Admon
Arie
A
Department of Biology, Technion, Haifa 32000, Israel. admon@tx.technion.ac.il
Barnea
Eilon
E
Ziv
Tamar
T
D000951:Antigens, Neoplasm / Q000032:analysis* / Q000276:immunology; D019496:Cancer Vaccines; D006801:Humans; D007167:Immunotherapy; D008285:Major Histocompatibility Complex / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology / Q000628:therapy; D010455:Peptides / Q000032:analysis*; D020543:Proteome / Q000032:analysis* / Q000276:immunology; D040901:Proteomics
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D010455:Peptides; D020543:Proteome