Immunoproteomic discovery of novel T cell antigens from the obligate intracellular pathogen Chlamydia.
Chlamydia infections cause substantial morbidity worldwide and effective prevention will depend on a vaccine. Since Chlamydia immunity is T cell-mediated, a major impediment to developing a molecular vaccine has been the difficulty in identifying relevant T cell Ags. In this study, we used a combination of affinity chromatography and tandem mass spectrometry to identify 13 Chlamydia peptides among 331 self-peptides presented by MHC class II (I-A(b)) molecules from bone marrow-derived murine dendritic cells infected with Chlamydia muridarum. These MHC class II-bound peptides were recognized by Chlamydia-specific CD4 T cells harvested from immune mice and adoptive transfer of dendritic cells pulsed ex vivo with the peptides partially protected mice against intranasal and genital tract Chlamydia infection. The results provide evidence for lead vaccine candidates for a T cell-based subunit molecular vaccine against Chlamydia infection suitable for human study.
Karunakaran
Karuna P
KP
British Columbia Centre for Disease Control, 655 West 12th Avenue, Vancouver, BC, Canada.
Rey-Ladino
Jose
J
Stoynov
Nikolay
N
Berg
Kyra
K
Shen
Caixia
C
Jiang
Xiaozhou
X
Gabel
Brent R
BR
Yu
Hong
H
Foster
Leonard J
LJ
Brunham
Robert C
RC
D000595:Amino Acid Sequence; D000818:Animals; D000942:Antigens, Bacterial / Q000302:isolation & purification* / Q000378:metabolism / Q000627:therapeutic use; D000945:Antigens, Differentiation, T-Lymphocyte / Q000302:isolation & purification* / Q000378:metabolism / Q000627:therapeutic use; D002478:Cells, Cultured; D002690:Chlamydia Infections / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D023502:Chlamydia muridarum / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D005260:Female; D006183:H-2 Antigens / Q000302:isolation & purification / Q000378:metabolism; D006367:HeLa Cells; D000949:Histocompatibility Antigens Class II / Q000302:isolation & purification / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D007424:Intracellular Fluid / Q000737:chemistry / Q000276:immunology* / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010455:Peptides / Q000302:isolation & purification / Q000378:metabolism / Q000627:therapeutic use; D011485:Protein Binding / Q000276:immunology; D020543:Proteome / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism; D053719:Tandem Mass Spectrometry
D000942:Antigens, Bacterial; D000945:Antigens, Differentiation, T-Lymphocyte; D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II; D010455:Peptides; D020543:Proteome