Anthrax lethal toxin and the induction of CD4 T cell immunity.
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.
['Ascough|Stephanie|S|', 'Ingram|Rebecca J|RJ|', 'Altmann|Daniel M|DM|']
D000818:Animals D022122:Anthrax Vaccines D000942:Antigens, Bacterial D001408:Bacillus anthracis D001427:Bacterial Toxins D015496:CD4-Positive T-Lymphocytes D018984:Epitopes, T-Lymphocyte D006801:Humans D007109:Immunity D020935:MAP Kinase Signaling System D008264:Macrophages D020929:Mitogen-Activated Protein Kinase Kinases D011487:Protein Conformation D015398:Signal Transduction
anthrax CD4 T cell protective antigen lethal factor epitope vaccine