Development of a mass spectrometry based method for the identification of gp96-chaperoned peptides destined for presentation in MHC class I molecules

• Main Author: Jackson, Angela M.
• Other Authors: Pearson, Terry W.
• Language: English; en
• Published: 2010
• Subjects: theileria parva; peptides; UVic Subject Index::Sciences and Engineering::Biology::Microbiology; UVic Subject Index::Sciences and Engineering::Chemistry::Biochemistry
• Online Access: http://hdl.handle.net/1828/2266

Theileria parva is an intracellular protozoan parasite and the causative agent of the lethal livestock disease East Coast fever (ECF). Research has shown that a protective cell-mediated immune response against parasite-infected lymphocytes is capable of clearing the host of T. parva (Pearson et al. 1979), leaving the host solidly immune to reinfection. The work presented in this thesis describes my attempts to develop a method for identification of major histocompatibility complex class I-associated T. parva peptides involved in eliciting this protective cell-mediated immune response. The soluble chaperone gp96 interacts with peptides destined for association with major histocompatibily complex class I molecules and is therefore a source of T. parva peptides that interact with extracellular immune effectors. Using sensitive mass spectrometry methods the gp96-chaperoned peptide proteome from model parasite infected T lymphocytes was compared to an uninfected T cell line. With our findings we have demonstrated proof of concept for a highly sensitive method for the elucidation of potentially immunogenic peptides capable of initiating a protective immune response against the intracellular parasite T parva.