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Anthrax Lethal Toxin and the Induction of CD4 T Cell Immunity
Section of Infectious Diseases & Immunity, Department of Medicine, Imperial College, Hammersmith Hospital, Du Cane Road, London, W12 0NN, UK
Centre for Infection and Immunity, Queen’s University Belfast, Health Sciences Building, 97 Lisburn Road, Belfast, BT9 7AE, UK
* Author to whom correspondence should be addressed.
Received: 30 July 2012; in revised form: 8 October 2012 / Accepted: 10 October 2012 / Published: 19 October 2012
Abstract: Bacillus anthracis secretes exotoxins which act through several mechanisms including those that can subvert adaptive immunity with respect both to antigen presenting cell and T cell function. The combination of Protective Antigen (PA) and Lethal Factor (LF) forming Lethal Toxin (LT), acts within host cells to down-regulate the mitogen activated protein kinase (MAPK) signaling cascade. Until recently the MAPK kinases were the only known substrate for LT; over the past few years it has become evident that LT also cleaves Nlrp1, leading to inflammasome activation and macrophage death. The predicted downstream consequences of subverting these important cellular pathways are impaired antigen presentation and adaptive immunity. In contrast to this, recent work has indicated that robust memory T cell responses to B. anthracis antigens can be identified following natural anthrax infection. We discuss how LT affects the adaptive immune response and specifically the identification of B. anthracis epitopes that are both immunogenic and protective with the potential for inclusion in protein sub-unit based vaccines.
Keywords: anthrax; lethal factor; protective antigen; CD4 T cell; vaccine; epitope
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MDPI and ACS Style
Ascough, S.; Ingram, R.J.; Altmann, D.M. Anthrax Lethal Toxin and the Induction of CD4 T Cell Immunity. Toxins 2012, 4, 878-899.
Ascough S, Ingram RJ, Altmann DM. Anthrax Lethal Toxin and the Induction of CD4 T Cell Immunity. Toxins. 2012; 4(10):878-899.
Ascough, Stephanie; Ingram, Rebecca J.; Altmann, Daniel M. 2012. "Anthrax Lethal Toxin and the Induction of CD4 T Cell Immunity." Toxins 4, no. 10: 878-899.