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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| Format: | Article |
| Language: | English |
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MDPI AG
2012-12-01
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| Series: | Toxins |
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| Online Access: | http://www.mdpi.com/2072-6651/4/12/1451 |
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| author | Judith A. James A. Darise Farris Melissa L. Nguyen Philip M. Cox Sherry R. Crowe Eric K. Dumas Sridevi Kurella Jonathan J. Hunt Lori Garman |
| author_facet | Judith A. James A. Darise Farris Melissa L. Nguyen Philip M. Cox Sherry R. Crowe Eric K. Dumas Sridevi Kurella Jonathan J. Hunt Lori Garman |
| author_sort | Judith A. James |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T21:33:52Z |
| format | Article |
| id | doaj.art-4e1fcabc602e409b9a1e6fb335510e5a |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-04-11T21:33:52Z |
| publishDate | 2012-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-4e1fcabc602e409b9a1e6fb335510e5a2022-12-22T04:01:50ZengMDPI AGToxins2072-66512012-12-014121451146710.3390/toxins4121451MHC Class II and Non-MHC Class II Genes Differentially Influence Humoral Immunity to Bacillus anthracis Lethal Factor and Protective AntigenJudith A. JamesA. Darise FarrisMelissa L. NguyenPhilip M. CoxSherry R. CroweEric K. DumasSridevi KurellaJonathan J. HuntLori GarmanAnthrax 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.http://www.mdpi.com/2072-6651/4/12/1451Bacillus anthracisprotective antigenlethal factorvaccineantibody responseMHC class IImousegenetic background |
| spellingShingle | Judith A. James A. Darise Farris Melissa L. Nguyen Philip M. Cox Sherry R. Crowe Eric K. Dumas Sridevi Kurella Jonathan J. Hunt Lori Garman MHC Class II and Non-MHC Class II Genes Differentially Influence Humoral Immunity to Bacillus anthracis Lethal Factor and Protective Antigen Toxins Bacillus anthracis protective antigen lethal factor vaccine antibody response MHC class II mouse genetic background |
| title | MHC Class II and Non-MHC Class II Genes Differentially Influence Humoral Immunity to Bacillus anthracis Lethal Factor and Protective Antigen |
| title_full | MHC Class II and Non-MHC Class II Genes Differentially Influence Humoral Immunity to Bacillus anthracis Lethal Factor and Protective Antigen |
| title_fullStr | MHC Class II and Non-MHC Class II Genes Differentially Influence Humoral Immunity to Bacillus anthracis Lethal Factor and Protective Antigen |
| title_full_unstemmed | MHC Class II and Non-MHC Class II Genes Differentially Influence Humoral Immunity to Bacillus anthracis Lethal Factor and Protective Antigen |
| title_short | MHC Class II and Non-MHC Class II Genes Differentially Influence Humoral Immunity to Bacillus anthracis Lethal Factor and Protective Antigen |
| title_sort | mhc class ii and non mhc class ii genes differentially influence humoral immunity to bacillus anthracis lethal factor and protective antigen |
| topic | Bacillus anthracis protective antigen lethal factor vaccine antibody response MHC class II mouse genetic background |
| url | http://www.mdpi.com/2072-6651/4/12/1451 |
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