Outer membrane proteins preferentially load MHC class II peptides: implications for a Chlamydia trachomatis T cell vaccine.
CD4 T cell immune responses such as interferon-γ and tumor necrosis factor-α secretion are necessary for Chlamydia immunity. We used an immunoproteomic approach in which Chlamydia trachomatis and Chlamydia muridarum-derived peptides presented by MHC class II molecules on the surface of infected dendritic cells (DCs) were identified by tandem mass spectrometry using bone marrow derived DCs (BMDCs) from mice of different MHC background. We first compared the C. muridarum immunoproteome in C3H mice to that previously identified in C57BL/6 mice. Fourteen MHC class II binding peptides from 11 Chlamydia proteins were identified from C3H infected BMDCs. Two C. muridarum proteins overlapped between C3H and C57B/6 mice and both were polymorphic membrane proteins (Pmps) which presented distinct class II binding peptides. Next we studied DCs from C57BL/6 mice infected with the human strain, C. trachomatis serovar D. Sixty MHC class II binding peptides derived from 27 C. trachomatis proteins were identified. Nine proteins were orthologous T cell antigens between C. trachomatis and C. muridarum and 2 of the nine were Pmps which generated MHC class II binding epitopes at distinct sequences within the proteins. As determined by antigen specific splenocyte responses outer membrane proteins PmpF, -G and -H and the major outer membrane protein (MOMP) were antigenic in mice previously infected with C. muridarum or C. trachomatis. Furthermore a recombinant protein vaccine consisting of the four Pmps (PmpEFGH) with MOMP formulated with a Th1 polarizing adjuvant significantly accelerated (p<0.001) clearance in the C57BL/6 mice C. trachomatis transcervical infection model. We conclude that Chlamydia outer membrane proteins are important T cell antigens useful in the development of a C. trachomatis subunit vaccine.
Vaccine Research Laboratory, University of British Columbia Centre for Disease Control, Vancouver, BC, Canada.
Karuna P
KP
Karunakaran
Vaccine Research Laboratory, University of British Columbia Centre for Disease Control, Vancouver, BC, Canada.
Hong
H
Yu
Vaccine Research Laboratory, University of British Columbia Centre for Disease Control, Vancouver, BC, Canada.
Xiaozhou
X
Jiang
Department of Biochemistry and Molecular Biology, Centre for High-Throughput Biology, University of British Columbia, Vancouver, BC, Canada.
Queenie
Q
Chan
Department of Biochemistry and Molecular Biology, Centre for High-Throughput Biology, University of British Columbia, Vancouver, BC, Canada.
Kyung-Mee
KM
Moon
Department of Biochemistry and Molecular Biology, Centre for High-Throughput Biology, University of British Columbia, Vancouver, BC, Canada.
Leonard J
LJ
Foster
Vaccine Research Laboratory, University of British Columbia Centre for Disease Control, Vancouver, BC, Canada. Electronic address: robert.brunham@bccdc.ca.
Robert C
RC
Brunham
D000276:Adjuvants, Immunologic; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000276:immunology*; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002690:Chlamydia Infections / Q000276:immunology*; D023502:Chlamydia muridarum / Q000737:chemistry / Q000276:immunology; D002692:Chlamydia trachomatis / Q000737:chemistry / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000276:immunology*; D040901:Proteomics; D053719:Tandem Mass Spectrometry; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology
D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D010455:Peptides; D014614:Vaccines, Synthetic
Antigen; Chlamydia; Epitope; Immunoproteomics; MHC; Outer membrane proteins; Peptide; T cell; Vaccine