PMID:19233475

Citation	Valentino, MD, Hensley, LL, Skrombolas, D, McPherson, PL, Woolard, MD, Kawula, TH, Frelinger, JA and Frelinger, JG (2009) Identification of a dominant CD4 T cell epitope in the membrane lipoprotein Tul4 from Francisella tularensis LVS. Mol. Immunol. 46:1830-8
Abstract	Francisella tularensis is a gram-negative intracellular bacterium that is the causative agent of tularemia. Small mammals such as rodents and rabbits, as well as some biting arthropods, serve as the main vectors for environmental reservoirs of F. tularensis. The low infectious dose, ability to aerosolize the organism, and the possibility of generating antibiotic resistant strains make F. tularensis a prime organism for use in bioterrorism. As a result, some strains of F. tularensis have been placed on the CDC category A select agent list. T cell immune responses are thought to be a critical component in protective immunity to this organism. However, investigation into the immune responses to F. tularensis has been hampered by the lack of molecularly defined epitopes. Here we report the identification of a major CD4(+) T cell epitope in C57Bl/6 (B6) mice. The murine model of F. tularensis infection is relevant as mice are a natural host for F. tularensis LVS and exhibit many of the same features of tularemia seen in humans. Using T cell hybridomas derived from B6 mice that had either been inoculated with F. tularensis and allowed to clear the infection or which had been immunized by conventional means using purified recombinant protein in adjuvant, we have identified amino acids 86-99 of the lipoprotein Tul4 (RLQWQAPEGSKCHD) as an immunodominant CD4 T cell epitope in B6 mice. This epitope is a major component of both the acute and memory responses to F. tularensis infection and can constitute as much as 20% of the responding CD4 T cells in an acute infection. Reactive T cells can also effectively enter the long-term memory T cell pool. The identification of this epitope will greatly aid in monitoring the course of F. tularensis infection and will also aid in the development of effective vaccine strategies for F. tularensis.
Links	PubMed PMC2709240 Online version:10.1016/j.molimm.2009.01.008
Keywords	Amino Acid Sequence; Animals; Bacterial Proteins/genetics; Bacterial Proteins/immunology; CD4-Positive T-Lymphocytes/immunology; Cells, Cultured; Epitope Mapping; Epitopes, T-Lymphocyte/genetics; Epitopes, T-Lymphocyte/immunology; Epitopes, T-Lymphocyte/isolation & purification; Francisella tularensis/immunology; Hybridomas/immunology; Immunodominant Epitopes/genetics; Immunodominant Epitopes/immunology; Immunodominant Epitopes/isolation & purification; Immunologic Memory/physiology; Lipoproteins/genetics; Lipoproteins/immunology; Membrane Proteins/genetics; Membrane Proteins/immunology; Mice; Mice, Inbred C57BL; Mice, Knockout; Tularemia/immunology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
FRATL:Q7X168		GO:0002437: inflammatory response to antigenic stimulus	ECO:0000314:		P		Figure 6: Tul4 was recognized during acute infections - examined the F. tularensis specific IFNγ responses of mice after intradermal inoculation with tularensis LVS. Splenocytes were isolated and stimulated in vitro for 18–24 h with Tul4 86–99 peptide. Cells were then stained using an array of cellular markers followed by analysis via multicolor flow cytometry, which allowed for identification of activated IFNγ positive CD4+ T cells.	complete CACAO 9074

References

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