title: Anthrax lethal toxin and the induction of CD4 T cell immunity.
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.
authors.affiliation: Section of Infectious Diseases & Immunity, Department of Medicine, Imperial College, Hammersmith Hospital, London, UK. s.ascough@imperial.ac.uk
authors.forename: Stephanie
authors.initials: S
authors.lastname: Ascough
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Ingram
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Altmann
mesh_terms: D000818:Animals; D022122:Anthrax Vaccines / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology* / Q000633:toxicity*; D001408:Bacillus anthracis / Q000276:immunology; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000633:toxicity*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006801:Humans; D007109:Immunity / Q000187:drug effects / Q000276:immunology; D020935:MAP Kinase Signaling System / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D020929:Mitogen-Activated Protein Kinase Kinases / Q000276:immunology / Q000378:metabolism; D011487:Protein Conformation; D015398:Signal Transduction
chemical_list: D022122:Anthrax Vaccines; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D018984:Epitopes, T-Lymphocyte; C030325:anthrax toxin; D020929:Mitogen-Activated Protein Kinase Kinases