title: Natural exposure to cutaneous anthrax gives long-lasting T cell immunity encompassing infection-specific epitopes.
abstract: There has been a long history of defining T cell epitopes to track viral immunity and to design rational vaccines, yet few data of this type exist for bacterial infections. Bacillus anthracis, the causative agent of anthrax, is both an endemic pathogen in many regions and a potential biological warfare threat. T cell immunity in naturally infected anthrax patients has not previously been characterized, which is surprising given concern about the ability of anthrax toxins to subvert or ablate adaptive immunity. We investigated CD4 T cell responses in patients from the Kayseri region of Turkey who were previously infected with cutaneous anthrax. Responses to B. anthracis protective Ag and lethal factor (LF) were investigated at the protein, domain, and epitope level. Several years after antibiotic-treated anthrax infection, strong T cell memory was detectable, with no evidence of the expected impairment in specific immunity. Although serological responses to existing anthrax vaccines focus primarily on protective Ag, the major target of T cell immunity in infected individuals and anthrax-vaccinated donors was LF, notably domain IV. Some of these anthrax epitopes showed broad binding to several HLA class alleles, but others were more constrained in their HLA binding patterns. Of specific CD4 T cell epitopes targeted within LF domain IV, one is preferentially seen in the context of bacterial infection, as opposed to vaccination, suggesting that studies of this type will be important in understanding how the human immune system confronts serious bacterial infection.
authors.affiliation: Department of Infectious Diseases and Immunity, Imperial College London, London, United Kingdom.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Ingram
authors.forename: Gökhan
authors.initials: G
authors.lastname: Metan
authors.forename: Bernard
authors.initials: B
authors.lastname: Maillere
authors.forename: Mehmet
authors.initials: M
authors.lastname: Doganay
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Ozkul
authors.forename: Louise U
authors.initials: LU
authors.lastname: Kim
authors.forename: Les
authors.initials: L
authors.lastname: Baillie
authors.forename: Hugh
authors.initials: H
authors.lastname: Dyson
authors.forename: E Diane
authors.initials: ED
authors.lastname: Williamson
authors.forename: Karen K
authors.initials: KK
authors.lastname: Chu
authors.forename: Stephanie
authors.initials: S
authors.lastname: Ascough
authors.forename: Steven
authors.initials: S
authors.lastname: Moore
authors.forename: Theresa B
authors.initials: TB
authors.lastname: Huwar
authors.forename: John H
authors.initials: JH
authors.lastname: Robinson
authors.forename: Shiranee
authors.initials: S
authors.lastname: Sriskandan
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Altmann
mesh_terms: D000881:Anthrax / Q000276:immunology*; D022122:Anthrax Vaccines / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology*; D001408:Bacillus anthracis / Q000276:immunology; D001427:Bacterial Toxins / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory
chemical_list: D022122:Anthrax Vaccines; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D018984:Epitopes, T-Lymphocyte; C030325:anthrax toxin