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Vaccination with APOB100 derived HLA-A2 restricted CD8 T cell epitopes did not reduce atherosclerosis in male LDLRKO HAPOB100TG HLA-A2TG mice
CD8 T cells make up a large amount of lymphocytes in atherosclerotic plaques, however their role in atherosclerosis has not been thoroughly studied. Since ApoB100 is a key antigen in atherosclerosis and a plausible vaccination target, we were interested in the role of ApoB100 specific CD8 T cells in atherosclerosis. To be directly relevant for human vaccination HLA-A2 transgenic (HLA-A2) and human ApoB100 transgenic (hApoB100tg) mice were used.
HLA-A2 restricted CD8 T cell epitopes derived from human ApoB100 were in silico predicted using The “Proteasomal cleavage/TAP transport/MHC class I combined predictor”of the immune epitope database. Best 6 epitopes were synthesized and binding to HLA-A2 assesed with T2 cell binding assays. To assess induction of peptide specific CD8 T cells, HLA-A2 transgenic mice were vaccinated with peptide pulsed DCs. Peptide recall responses were measured with flow cytometry. To study whether vaccination with ApoB100 derived CD8 T cell epitopes could influence atherosclerosis, male hApoB100tg HLA-A2tg LDLrKO mice (n=10-11) were vaccinated with peptide pulsed bone marrow derived DCs and boosted a week later with with αCD40 and Poly(I:C) and peptides. Animals were fed western type diet for 11 weeks following DC vaccination, after which they were sacrificed to assess aortic root lesion development.
All predicted HLA-A2 restricted CD8 T cell epitopes stabilized HLA-A2 in T2 cell binding assays, indicating binding of all peptides to HLA-A2. For 5 of 6 peptides peptide specific recall response were measured a week after vaccination with peptide pulsed DCs. Vaccination with these CD8 T cell epitopes did not lead to reduced atherosclerosis. 10 weeks after the booster vaccination still peptide specific CD8 T cell responses could be detected, indicating that the vaccination was succesful.
We have identified 5 HLA-A2 restricted ApoB100 derived CD8 T cell epitopes. Vaccination with these peptides did induce long lasting ApoB100 specific CD8 T cells, however did not affect atherosclerosis in male hApoB100tg HLA-A2tg LDLrKO mice
- All authors
- Schaftenaar, F.H.; Amersfoort, J.; Douna, H.; Kroner, M.J.; Slutter, B.A.; Bot, I.; Puijvelde, G.H.M. van; Kuiper, J.
- Date
- 2018-06-30
- Volume
- 32
- Pages
- 100 - 101