Outer membrane proteins preferentially load MHC class II peptides: Implications for a Chlamydia trachomatis T cell vaccine

ABSTRACT We used a photoactivatable, lipophilic reagent, 3′-(trifluoromethyl)-3-(m-[125I]iodophenyl)diazirine, to label proteins in the outer membrane of elementary bodies ofChlamydia trachomatis LGV serovar L2 and mass spectrometry to identify the labeled proteins. The identified proteins were polymorphic outer membrane proteins E, G, and H, which were made late in the developmental cycle, the major outer membrane protein, and a mixture of 46-kDa proteins consisting of the open reading frame 623 protein and possibly a modified form of the major outer membrane protein.

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Development of a Chlamydia trachomatis T cell Vaccine

Human Vaccines ◽

10.4161/hv.6.8.12299 ◽

2010 ◽

Vol 6 (8) ◽

pp. 676-680 ◽

Cited By ~ 21

Author(s):

Karuna P. Karunakaran ◽

Hong Yu ◽

Leonard J. Foster ◽

Robert C. Brunham

Keyword(s):

T Cell ◽

Chlamydia Trachomatis ◽

Cell Vaccine ◽

T Cell Vaccine

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Physical Linkage of Naturally Complexed Bacterial Outer Membrane Proteins Enhances Immunogenicity

Infection and Immunity ◽

10.1128/iai.01356-07 ◽

2007 ◽

Vol 76 (3) ◽

pp. 1223-1229 ◽

Cited By ~ 19

Author(s):

Henriette Macmillan ◽

Junzo Norimine ◽

Kelly A. Brayton ◽

Guy H. Palmer ◽

Wendy C. Brown

Keyword(s):

T Cell ◽

Membrane Proteins ◽

Outer Membrane ◽

Outer Membrane Proteins ◽

Surface Protein ◽

Host Cells ◽

Effective Vaccine ◽

T Cell Epitopes ◽

Carrier Effect ◽

Major Surface

ABSTRACTThe outer membrane proteins (OMPs) of bacterial pathogens are essential for their growth and survival and especially for attachment and invasion of host cells. Since the outer membrane is the interface between the bacterium and the host cell, outer membranes and individual OMPs are targeted for development of vaccines against many bacterial diseases. Whole outer membrane fractions often protect against disease, and this protection cannot be fully reproduced by using individual OMPs. Exactly how the interactions among individual OMPs influence immunity is not well understood. We hypothesized that one OMP rich in T-cell epitopes can act as a carrier for an associated OMP which is poor in T-cell epitopes to generate T-dependent antibody responses, similar to the hapten-carrier effect. Major surface protein 1a (MSP1a) and MSP1b1 occur as naturally complexed OMPs in theAnaplasma marginaleouter membrane. Previous studies demonstrated that immunization with the native MSP1 heteromer induced strong immunoglobulin G (IgG) responses to both proteins, but only MSP1a stimulated strong CD4+T-cell responses. Therefore, to test our hypothesis, constructs of CD4+T-cell epitopes from MSP1a linked to MSP1b1 were compared with individually administered MSP1a and MSP1b1 for induction of MSP1b-specific IgG. By linking the T-cell epitopes from MSP1a to MSP1b1, significantly higher IgG titers against MSP1b1 were induced. Understanding how the naturally occurring intermolecular interactions between OMPs influence the immune response may lead to more effective vaccine design.

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