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Infection and Immunity, November 2005, p. 7226-7235, Vol. 73, No. 11
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.11.7226-7235.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

CD4+-T-Cell Responses Generated during Murine Salmonella enterica Serovar Typhimurium Infection Are Directed towards Multiple Epitopes within the Natural Antigen FliC

Molly A. Bergman,1,{dagger} Lisa A. Cummings,2 Robert C. Alaniz,2 Laura Mayeda,2 Ivana Fellnerova,2 and Brad T. Cookson1,2*

Departments of Microbiology,1 Laboratory Medicine, University of Washington, Seattle, Washington2

Received 29 March 2005/ Returned for modification 5 July 2005/ Accepted 1 August 2005

The flagellar filament protein FliC is a natural antigen recognized by memory CD4+ T cells recovered from Salmonella enterica serovar Typhimurium-infected humans and mice. To further investigate T-cell responses to FliC, we derived FliC-specific CD4+-T-cell clones from mice of two different haplotypes following oral S. enterica serovar Typhimurium infection. Using C-terminal truncations of MalE-FliC recombinant fusion proteins, we mapped antigenic activity to four different regions of FliC; three of the four epitope-containing regions were present in both FliC and the alternate flagellin subunit FljB. We determined that two novel FliC epitopes were also present in flagellins from several gram-negative enteric bacterial species: Ek-restricted FliC 80-94 (amino acids 80 to 94) and Ab-restricted FliC 455-469. Further mapping confirmed the presence of two previously identified FliC epitopes: Ak-restricted FliC 339-350 and Ab-restricted FliC 428-442. Therefore, like the recognition site of the innate immune receptor Toll-like receptor 5, three of four FliC epitopes recognized by CD4+ T cells colocalize in the D0/D1 domains of FliC. Salmonella-infected macrophages and dendritic cells stimulated epitope-specific CD4+-T-cell proliferation; infected dendritic cells also activated T cells to produce gamma interferon. These data demonstrate that Salmonella infection generates murine CD4+-T-cell responses to multiple epitopes in the natural antigen FliC and that recognition of infected phagocytes by FliC-specific CD4+ T cells triggers effector functions known to be essential for protective immunity. Together, these data suggest that FliC-specific CD4+ T cells may contribute to cell-mediated host defenses against Salmonella.

* Corresponding author. Mailing address: Departments of Laboratory Medicine and Microbiology, University of Washington Medical Center, Box 357110, 1959 NE Pacific Street, Seattle, WA 98195. Phone: (206) 598-6131. Fax: (206) 598-6189. E-mail: cookson{at}u.washington.edu.

Editor: V. J. DiRita

{dagger} Present address: Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA 02112.

Infection and Immunity, November 2005, p. 7226-7235, Vol. 73, No. 11
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.11.7226-7235.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Alaniz, R. C., Deatherage, B. L., Lara, J. C., Cookson, B. T. (2007). Membrane Vesicles Are Immunogenic Facsimiles of Salmonella typhimurium That Potently Activate Dendritic Cells, Prime B and T Cell Responses, and Stimulate Protective Immunity In Vivo. J. Immunol. 179: 7692-7701 [Abstract] [Full Text]  
  • Alaniz, R. C., Cummings, L. A., Bergman, M. A., Rassoulian-Barrett, S. L., Cookson, B. T. (2006). Salmonella typhimurium Coordinately Regulates FliC Location and Reduces Dendritic Cell Activation and Antigen Presentation to CD4+ T cells. J. Immunol. 177: 3983-3993 [Abstract] [Full Text]  
  • Sanders, C. J., Yu, Y., Moore, D. A. III, Williams, I. R., Gewirtz, A. T. (2006). Humoral immune response to flagellin requires T cells and activation of innate immunity.. J. Immunol. 177: 2810-2818 [Abstract] [Full Text]  


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