Identification of MHC-Bound Peptides from Dendritic Cells Infected with Salmonella enterica Strain SL1344: Implications for a Nontyphoidal Salmonella Vaccine.
Worldwide Salmonella enterica infections result in substantial morbidity and mortality and are the major cause of infant bacteremia in Sub-Saharan Africa. Diseases caused by Salmonella 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 Salmonella depends primarily on CD4 T-cell-mediated immune responses; therefore, identifying relevant T-cell antigens is necessary for Salmonella 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 Chlamydia 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 Salmonella enterica 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 Salmonella-derived peptides. Four of the 12 highest scoring class-II-binding Salmonella peptides stimulated IFN-γ production by CD4+T cells from the spleens of mice with persistent Salmonella infection. We conclude that antigens identified by MHC immunoproteomics will be useful for Salmonella immunobiology studies and are potential Salmonella vaccine candidates. Data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the data set identifier PXD004451.
Vaccine Research Laboratory, University of British Columbia Centre for Disease Control , Vancouver, British Columbia V5Z 4R4, Canada.
Karuna P
KP
Karunakaran
Vaccine Research Laboratory, University of British Columbia Centre for Disease Control , Vancouver, British Columbia V5Z 4R4, Canada.
Hong
H
Yu
Vaccine Research Laboratory, University of British Columbia Centre for Disease Control , Vancouver, British Columbia V5Z 4R4, Canada.
Xiaozhou
X
Jiang
Department of Biochemistry and Molecular Biology, Centre for High-Throughput Biology, University of British Columbia , Vancouver, British Columbia V6T 1Z3, Canada.
Queenie
Q
Chan
Center for Immunology, Department of Microbiology and Immunology, University of Minnesota Medical School , Minneapolis, Minnesota 55455, United States.
Michael F
MF
Goldberg
Center for Immunology, Department of Microbiology and Immunology, University of Minnesota Medical School , Minneapolis, Minnesota 55455, United States.
Marc K
MK
Jenkins
Department of Biochemistry and Molecular Biology, Centre for High-Throughput Biology, University of British Columbia , Vancouver, British Columbia V6T 1Z3, Canada.
Leonard J
LJ
Foster
Vaccine Research Laboratory, University of British Columbia Centre for Disease Control , Vancouver, British Columbia V5Z 4R4, Canada.
Robert C
RC
Brunham
D000595:Amino Acid Sequence; D000818:Animals; D000942:Antigens, Bacterial / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D001854:Bone Marrow Cells / Q000276:immunology / Q000382:microbiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000382:microbiology; D002846:Chromatography, Affinity; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D012480:Salmonella Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D022562:Salmonella Vaccines / Q000008:administration & dosage / Q000096:biosynthesis*; D019779:Salmonella enterica / Q000276:immunology*; D013154:Spleen / Q000276:immunology / Q000382:microbiology
D000942:Antigens, Bacterial; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D010455:Peptides; D022562:Salmonella Vaccines; D007371:Interferon-gamma
MHC; Salmonella; T cell; antigen; epitope; immunoproteomics; peptide; vaccine