Toxins 2012, 4(12), 1451-1467; doi:10.3390/toxins4121451
Article

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

Lori Garman 1,2 email, Eric K. Dumas 1,2 email, Sridevi Kurella 1 email, Jonathan J. Hunt 2 email, Sherry R. Crowe 1 email, Melissa L. Nguyen 1,2 email, Philip M. Cox 1 email, Judith A. James 1,2,3 email and A. Darise Farris 1,2,* email
1 Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA 2 Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, 940 Stanton L. Young Blvd, Oklahoma City, OK 73104, USA 3 Departments of Medicine and Pathology, University of Oklahoma Health Sciences Center, 1000 Stanton L. Young Blvd, Oklahoma City, OK 73104, USA
* Author to whom correspondence should be addressed.
Received: 22 August 2012; in revised form: 16 November 2012 / Accepted: 28 November 2012 / Published: 5 December 2012
(This article belongs to the Special Issue Toxin-Antibody Interactions)
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Abstract: 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.
Keywords: Bacillus anthracis; protective antigen; lethal factor; vaccine; antibody response; MHC class II; mouse; genetic background

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MDPI and ACS Style

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.

AMA Style

Garman L, Dumas EK, Kurella S, Hunt JJ, Crowe SR, Nguyen ML, Cox PM, James JA, Farris AD. MHC Class II and Non-MHC Class II Genes Differentially Influence Humoral Immunity to Bacillus anthracis Lethal Factor and Protective Antigen. Toxins. 2012; 4(12):1451-1467.

Chicago/Turabian Style

Garman, Lori; Dumas, Eric K.; Kurella, Sridevi; Hunt, Jonathan J.; Crowe, Sherry R.; Nguyen, Melissa L.; Cox, Philip M.; James, Judith A.; Farris, A. Darise. 2012. "MHC Class II and Non-MHC Class II Genes Differentially Influence Humoral Immunity to Bacillus anthracis Lethal Factor and Protective Antigen." Toxins 4, no. 12: 1451-1467.

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