MHC class II and non-MHC class II genes differentially influence humoral immunity to Bacillus anthracis lethal factor and protective antigen

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 re...

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Bibliographic Details
Published in:Toxins 2012-12, Vol.4 (12), p.1451-1467
Main Authors: 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
Format: Article
Language:English
Subjects:
Animals
antibody response
Antigens, Bacterial - immunology
Bacillus anthracis
Bacterial Toxins - immunology
Epitope Mapping
Genes, MHC Class II
genetic background
Immunity, Humoral - genetics
Immunization
Immunoglobulin G - blood
lethal factor
MHC class II
Mice
Mice, Inbred C57BL
Mice, Inbred Strains
mouse
protective antigen
Recombinant Proteins - immunology
Toxins
vaccine
Vaccines
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Summary: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.
ISSN:2072-6651
2072-6651
DOI:10.3390/toxins4121451