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Baker, Teesha Crystal

University of British Columbia

The adaptive immune system relies on antigen presentation governed by major histocompatibility complexes (MHCs), which initiate immune responses upon recognition by T- lymphocytes. Vaccines are designed to create immunological memory by delivering pathogen- derived antigens. Understanding the preferences of MHCs for epitopes is essential for effective vaccine design. Current research lacks insights into why certain antigens, while strongly presented by one MHC allele, may not be recognized at all by others. This thesis investigates the binding preferences for MHC-II-presented peptides, providing a comprehensive understanding of antigen presentation across diverse MHC alleles. If we understand better which epitopes are best recognized and presented by MHCs then we will be able to design more effective vaccines. In the first data chapter, Mild Acid Elution (MAE) is demonstrated as an effective method for isolating MHC-II-presented immunopeptides. This method's potential advantages are highlighted, and the importance of additional separation techniques, such as ion mobility cells and offline reverse-phase chromatography, is emphasized for enhancing peptide identification. Insights into background contamination sources in MAE are explored, paving the way for cleaner data and more accurate immunopeptide identification. The second data chapter addresses the challenges posed by genetic diversity in vaccine development by strategically selecting a panel of 30 cell lines from the 1000 Genomes Project, ensuring global HLA diversity representation. This chapter unveils the intricate nature of antigen identification and binding predictions, emphasizing the unpredictability of immunopeptidomics, and underscoring the need for experimental validation in epitope prediction. The investigation into Salmonella enterica lysate exposure provides valuable insights into potential vaccine candidates and the efficient identification of MHC-presented immunopeptides. This research lays a foundation for leveraging immunopeptidomics in vaccine design and understanding antigen presentation, offering promising avenues for advancements in personalized medicine and vaccine development. In summary, this thesis unveils the potential of MAE for immunopeptide isolation, addresses the complexities of genetic diversity in vaccine development, and emphasizes the importance of experimental identification of vaccine targets.

Text

2024-02-26

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/87479

Biochemistry and Molecular Biology

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/