The use of mass spectrometry to identify antigens from proteasome processing.
Mass spectrometry (MS) is a powerful tool for the characterization of antigenic peptides that play a major role in the immune system. Most of the major histocompatibility complex (MHC) class I peptides are generated during the degradation of intracellular proteins by the proteasome, a catalytic complex present in all eukaryotic cells. This chapter focuses on the contribution of MS to the understanding of the mechanisms of antigen processing by the proteasome. This knowledge may be valuable for the design of specific inhibitors of proteasome, which has recently been recognized as a therapeutic target in cancer therapies and for the development of efficient peptidic vaccines in immunotherapies. Examples from the literature have been chosen to illustrate how MS data can contribute first to the understanding of the mechanisms of proteasomal processing and, second, to the understanding of the crucial role of proteasome in cytotoxic T lymphocytes (CTL) activation. The general strategy based on MS analyses used in these studies is also described.
Burlet-Schiltz
Odile
O
Institut de Pharmacologie et de Biologie Structurale, CNRS, Toulouse, France.
Claverol
Stéphane
S
Gairin
Jean Edouard
JE
Monsarrat
Bernard
B
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D000941:Antigens / Q000737:chemistry; D001671:Biochemistry / Q000379:methods; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D000939:Epitopes / Q000737:chemistry; D005805:Genes, MHC Class I; D006801:Humans; D007167:Immunotherapy; D013058:Mass Spectrometry / Q000379:methods*; D008954:Models, Biological; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry* / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013997:Time Factors; D014466:Ultraviolet Rays
D000941:Antigens; D000939:Epitopes; D010455:Peptides; D046988:Proteasome Endopeptidase Complex