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Open AccessArticle

MHC Class II and Non-MHC Class II Genes Differentially Influence Humoral Immunity to Bacillus anthracis Lethal Factor and Protective Antigen

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Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA
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Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, 940 Stanton L. Young Blvd, Oklahoma City, OK 73104, USA
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Departments of Medicine and Pathology, University of Oklahoma Health Sciences Center, 1000 Stanton L. Young Blvd, Oklahoma City, OK 73104, USA
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Author to whom correspondence should be addressed.
Toxins 2012, 4(12), 1451-1467; https://doi.org/10.3390/toxins4121451
Received: 22 August 2012 / Revised: 16 November 2012 / Accepted: 28 November 2012 / Published: 5 December 2012
(This article belongs to the Special Issue Toxin-Antibody Interactions)
Anthrax Lethal Toxin consists of Protective Antigen (PA) and Lethal Factor (LF), and current vaccination strategies focus on eliciting antibodies to PA. In human vaccination, the response to PA can vary greatly, and the response is often directed toward non-neutralizing epitopes. Variable vaccine responses have been shown to be due in part to genetic differences in individuals, with both MHC class II and other genes playing roles. Here, we investigated the relative contribution of MHC class II versus non-MHC class II genes in the humoral response to PA and LF immunization using three immunized strains of inbred mice: A/J (H-2k at the MHC class II locus), B6 (H-2b), and B6.H2k (H-2k). IgG antibody titers to LF were controlled primarily by the MHC class II locus, whereas IgG titers to PA were strongly influenced by the non-MHC class II genetic background. Conversely, the humoral fine specificity of reactivity to LF appeared to be controlled primarily through non-MHC class II genes, while the specificity of reactivity to PA was more dependent on MHC class II. Common epitopes, reactive in all strains, occurred in both LF and PA responses. These results demonstrate that MHC class II differentially influences humoral immune responses to LF and PA. View Full-Text
Keywords: Bacillus anthracis; protective antigen; lethal factor; vaccine; antibody response; MHC class II; mouse; genetic background Bacillus anthracis; protective antigen; lethal factor; vaccine; antibody response; MHC class II; mouse; genetic background
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Garman, L.; Dumas, E.K.; Kurella, S.; Hunt, J.J.; Crowe, S.R.; Nguyen, M.L.; Cox, P.M.; James, J.A.; Farris, A.D. MHC Class II and Non-MHC Class II Genes Differentially Influence Humoral Immunity to Bacillus anthracis Lethal Factor and Protective Antigen. Toxins 2012, 4, 1451-1467.

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