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Abstract

Antigen presentation by major histocompatibility complexes (MHCs) is essential for initiating a robust adaptive immune response. Vaccination leverages this process to induce immunological memory. However, the extensive polymorphism of MHC genes poses a challenge for subunit vaccine candidate selection, as individuals with different MHC alleles present distinct peptide repertoires. This diversity and variation in allele frequencies are evident across different populations and geographic regions. This study establishes mild acid elution as an effective method for isolating MHC-II-bound immunopeptides. With this workflow integrated with library data, the influence of MHC diversity is addressed by using a panel of cell lines and allele sets representative of the global population, enabling the identification of shared binding motifs. Peptides from Salmonella enterica, selected as the model pathogen, predicted to be broadly presented across diverse MHC alleles were examined for their ability to elicit immune responses, including T cell activation and antibody production. Biological samples collected from infected mouse models were assessed for T-cell activation using interferon-gamma enzyme-linked immunospot (ELISPOT) assays and for antibody responses using Immunoglobulin G (IgG) enzyme-linked immunosorbent (ELISA) assays. This thesis highlights the challenges posed by MHC diversity in vaccine development and presents a novel strategy that considers population-level variation from the outset of vaccine design. Among the tested candidate peptides, the outer membrane protein F (OmpF) peptide exhibited significantly higher IgG binding in the ELISA assay compared to the other peptides.