Identification of MHC-Bound Peptides from Dendritic Cells Infected with <i>Salmonella enterica</i> Strain SL1344: Implications for a Nontyphoidal <i>Salmonella</i> Vaccine

Worldwide <i>Salmonella enterica</i> infections result in substantial morbidity and mortality and are the major cause of infant bacteremia in Sub-Saharan Africa. Diseases caused by <i>Salmonella</i> are treatable with antibiotics, but successful antibiotic treatment has become difficult due to antimicrobial resistance and collateral effects on the microbiome. An effective vaccine together with public health efforts may be a better strategy to control these infections. Protective immunity against <i>Salmonella</i> depends primarily on CD4 T-cell-mediated immune responses; therefore, identifying relevant T-cell antigens is necessary for <i>Salmonella</i> vaccine development. We previously used a dendritic-cell-based immunoproteomics approach in our laboratory to identify T-cell antigens. The testing of these antigens as vaccine candidates against <i>Chlamydia</i> infection in mice yielded positive results. We applied this technology in the present study by infecting murine bone-marrow-derived dendritic cells from C57BL/6 mice with <i>Salmonella enterica</i> strain SL1344, followed by immunoaffinity isolation of MHC class I and II molecules and elution of bound peptides. The sequences of the peptides were identified using tandem mass spectrometry. We identified 87 MHC class-II- and 23 MHC class-I-binding <i>Salmonella</i>-derived peptides. Four of the 12 highest scoring class-II-binding <i>Salmonella</i> peptides stimulated IFN-γ production by CD4⁺ T cells from the spleens of mice with persistent <i>Salmonella</i> infection. We conclude that antigens identified by MHC immunoproteomics will be useful for <i>Salmonella</i> immunobiology studies and are potential <i>Salmonella</i> vaccine candidates. Data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the data set identifier PXD004451