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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1830-1838 |
| Number of pages | 9 |
| Journal | Molecular Immunology |
| Volume | 46 |
| Issue number | 8-9 |
| DOIs | |
| State | Published - May 2009 |
| Externally published | Yes |
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Keywords
- Epitope discovery
- Francisella tularensis
- T lymphocyte
- Tul4
ASJC Scopus subject areas
- Molecular Biology
- Immunology
Cite this
Identification of a dominant CD4 T cell epitope in the membrane lipoprotein Tul4 from Francisella tularensis LVS. / Valentino, Michael D.; Hensley, Lucinda L.; Skrombolas, Denise; McPherson, Pamela L.; Woolard, Matthew D.; Kawula, Thomas H.; Frelinger, Jeffrey A; Frelinger, John G.
In: Molecular Immunology, Vol. 46, No. 8-9, 05.2009, p. 1830-1838.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Identification of a dominant CD4 T cell epitope in the membrane lipoprotein Tul4 from Francisella tularensis LVS
AU - Valentino, Michael D.
AU - Hensley, Lucinda L.
AU - Skrombolas, Denise
AU - McPherson, Pamela L.
AU - Woolard, Matthew D.
AU - Kawula, Thomas H.
AU - Frelinger, Jeffrey A
AU - Frelinger, John G.
PY - 2009/5
Y1 - 2009/5
N2 - 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.
AB - 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.
KW - Epitope discovery
KW - Francisella tularensis
KW - T lymphocyte
KW - Tul4
UR - http://www.scopus.com/inward/record.url?scp=64149106283&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=64149106283&partnerID=8YFLogxK
U2 - 10.1016/j.molimm.2009.01.008
DO - 10.1016/j.molimm.2009.01.008
M3 - Article
C2 - 19233475
AN - SCOPUS:64149106283
VL - 46
SP - 1830
EP - 1838
JO - Molecular Immunology
JF - Molecular Immunology
SN - 0161-5890
IS - 8-9
ER -