Atheroprotective Vaccination with MHC-II Restricted Peptides from ApoB-100
Background: Subsets of CD4+ T-cells have been proposed to serve differential roles in the development of atherosclerosis. Some T-cell types are atherogenic (T-helper type 1), while others are thought to be protective (regulatory T-cells). Lineage commitment toward one type of helper T-cell versus an...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2013-12-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fimmu.2013.00493/full |
| _version_ | 1818543630856486912 |
|---|---|
| author | Kevin Yee-Bien Tse Ayelet eGonen John eSidney Hui eOuyang Joseph L Witztum Alessandro eSette Harley Y Tse Klaus eLey |
| author_facet | Kevin Yee-Bien Tse Ayelet eGonen John eSidney Hui eOuyang Joseph L Witztum Alessandro eSette Harley Y Tse Klaus eLey |
| author_sort | Kevin Yee-Bien Tse |
| collection | DOAJ |
| description | Background: Subsets of CD4+ T-cells have been proposed to serve differential roles in the development of atherosclerosis. Some T-cell types are atherogenic (T-helper type 1), while others are thought to be protective (regulatory T-cells). Lineage commitment toward one type of helper T-cell versus another is strongly influenced by the inflammatory context in which antigens are recognized. Immunization of atherosclerosis-prone mice with low density lipoprotein (LDL) or its oxidized derivative (ox-LDL) is known to be atheroprotective. However, the antigen specificity of the T-cells induced by vaccination and the mechanism of protection are not known.<br/>Methods: Identification of two peptide fragments (ApoB3501-3516 and ApoB978-993) from murine ApoB-100 was facilitated using I-Ab prediction models, and their binding to I-Ab determined. Utilizing a vaccination scheme based on complete and incomplete Freund’s adjuvant (1x CFA + 4x IFA), we immunized Apoe-/- mice with ApoB3501-3516 or ApoB978-993 emulsified in CFA once and subsequently boosted in IFA four times over 15 weeks. Spleens, lymph nodes and aortas were harvested and evaluated by flow cytometry and real time RT-PCR. Total atherosclerotic plaque burden was determined by aortic pinning and by aortic root histology.<br/>Results: Mice immunized with ApoB3501-3516 or ApoB978-993 demonstrated 40% reduction in overall plaque burden when compared to adjuvant only control mice. Aortic root frozen sections from ApoB3501-3516 immunized mice showed a >60% reduction in aortic sinus plaque development. Aortas from both ApoB3501-3516 and ApoB978-993 immunized mice contained significantly more mRNA for IL-10. Both antigen-specific IgG1 and IgG2c titers were elevated in ApoB3501-3516 or ApoB978-993 immunized mice, suggesting helper T-cell immune activity after immunization.<br/>Conclusion: Our data show that MHC Class II restricted ApoB-100 peptides can be atheroprotective, potentially through a mechanism involving elevated IL-10. |
| first_indexed | 2024-12-11T22:37:56Z |
| format | Article |
| id | doaj.art-ae5dc9697b3e49c0a98abb802771866c |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-11T22:37:56Z |
| publishDate | 2013-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-ae5dc9697b3e49c0a98abb802771866c2022-12-22T00:47:54ZengFrontiers Media S.A.Frontiers in Immunology1664-32242013-12-01410.3389/fimmu.2013.0049374978Atheroprotective Vaccination with MHC-II Restricted Peptides from ApoB-100Kevin Yee-Bien Tse0Ayelet eGonen1John eSidney2Hui eOuyang3Joseph L Witztum4Alessandro eSette5Harley Y Tse6Klaus eLey7University of California at San DiegoUniversity of California at San DiegoLa Jolla Institute for Allergy and ImmunologyLa Jolla Institute for Allergy and ImmunologyUniversity of California at San DiegoLa Jolla Institute for Allergy and ImmunologyWayne State UniversityLa Jolla Institute for Allergy and ImmunologyBackground: Subsets of CD4+ T-cells have been proposed to serve differential roles in the development of atherosclerosis. Some T-cell types are atherogenic (T-helper type 1), while others are thought to be protective (regulatory T-cells). Lineage commitment toward one type of helper T-cell versus another is strongly influenced by the inflammatory context in which antigens are recognized. Immunization of atherosclerosis-prone mice with low density lipoprotein (LDL) or its oxidized derivative (ox-LDL) is known to be atheroprotective. However, the antigen specificity of the T-cells induced by vaccination and the mechanism of protection are not known.<br/>Methods: Identification of two peptide fragments (ApoB3501-3516 and ApoB978-993) from murine ApoB-100 was facilitated using I-Ab prediction models, and their binding to I-Ab determined. Utilizing a vaccination scheme based on complete and incomplete Freund’s adjuvant (1x CFA + 4x IFA), we immunized Apoe-/- mice with ApoB3501-3516 or ApoB978-993 emulsified in CFA once and subsequently boosted in IFA four times over 15 weeks. Spleens, lymph nodes and aortas were harvested and evaluated by flow cytometry and real time RT-PCR. Total atherosclerotic plaque burden was determined by aortic pinning and by aortic root histology.<br/>Results: Mice immunized with ApoB3501-3516 or ApoB978-993 demonstrated 40% reduction in overall plaque burden when compared to adjuvant only control mice. Aortic root frozen sections from ApoB3501-3516 immunized mice showed a >60% reduction in aortic sinus plaque development. Aortas from both ApoB3501-3516 and ApoB978-993 immunized mice contained significantly more mRNA for IL-10. Both antigen-specific IgG1 and IgG2c titers were elevated in ApoB3501-3516 or ApoB978-993 immunized mice, suggesting helper T-cell immune activity after immunization.<br/>Conclusion: Our data show that MHC Class II restricted ApoB-100 peptides can be atheroprotective, potentially through a mechanism involving elevated IL-10.http://journal.frontiersin.org/Journal/10.3389/fimmu.2013.00493/fullAtherosclerosisVaccinationIL-10T-cellsApoB-100 Peptides |
| spellingShingle | Kevin Yee-Bien Tse Ayelet eGonen John eSidney Hui eOuyang Joseph L Witztum Alessandro eSette Harley Y Tse Klaus eLey Atheroprotective Vaccination with MHC-II Restricted Peptides from ApoB-100 Frontiers in Immunology Atherosclerosis Vaccination IL-10 T-cells ApoB-100 Peptides |
| title | Atheroprotective Vaccination with MHC-II Restricted Peptides from ApoB-100 |
| title_full | Atheroprotective Vaccination with MHC-II Restricted Peptides from ApoB-100 |
| title_fullStr | Atheroprotective Vaccination with MHC-II Restricted Peptides from ApoB-100 |
| title_full_unstemmed | Atheroprotective Vaccination with MHC-II Restricted Peptides from ApoB-100 |
| title_short | Atheroprotective Vaccination with MHC-II Restricted Peptides from ApoB-100 |
| title_sort | atheroprotective vaccination with mhc ii restricted peptides from apob 100 |
| topic | Atherosclerosis Vaccination IL-10 T-cells ApoB-100 Peptides |
| url | http://journal.frontiersin.org/Journal/10.3389/fimmu.2013.00493/full |
| work_keys_str_mv | AT kevinyeebientse atheroprotectivevaccinationwithmhciirestrictedpeptidesfromapob100 AT ayeletegonen atheroprotectivevaccinationwithmhciirestrictedpeptidesfromapob100 AT johnesidney atheroprotectivevaccinationwithmhciirestrictedpeptidesfromapob100 AT huieouyang atheroprotectivevaccinationwithmhciirestrictedpeptidesfromapob100 AT josephlwitztum atheroprotectivevaccinationwithmhciirestrictedpeptidesfromapob100 AT alessandroesette atheroprotectivevaccinationwithmhciirestrictedpeptidesfromapob100 AT harleyytse atheroprotectivevaccinationwithmhciirestrictedpeptidesfromapob100 AT klauseley atheroprotectivevaccinationwithmhciirestrictedpeptidesfromapob100 |