Identification of apoB-100 Peptide-Specific CD8+ T Cells in Atherosclerosis

T cells are found in atherosclerotic plaques, with evidence supporting a potential role for CD8+ T cells in atherogenesis. Prior studies provide evidence of low-density lipoprotein and apoB-100 reactive T cells, yet specific epitopes relevant to the disease remain to be defined. The current study was undertaken to identify and characterize endogenous, antigen-specific CD8+ T cells in atherosclerosis.

A peptide fragment of apoB-100 that tested positive for binding to the mouse MHC-I allele H2K^b was used to generate a fluorescent-labeled H2K^b pentamer and tested in apoE^-/- mice. H2K^b pentamer(+)CD8+ T cells were higher in apoE^-/- mice fed an atherogenic diet compared with those fed a normal chow. H2K^b pentamer (+)CD8+ T cells in atherogenic diet-fed mice had significantly increased effector memory phenotype with a shift in Vβ profile. H2K^b pentamer blocked lytic activity of CD8+ T cells from atherogenic diet-fed mice. Immunization of age-matched apoE^-/- mice with the apoB-100 peptide altered the immune-dominant epitope of CD8+ T cells and reduced atherosclerosis.

Our study provides evidence of a self-reactive, antigen-specific CD8+ T-cell population in apoE^-/- mice. Immune modulation using the peptide antigen reduced atherosclerosis in apoE^-/- mice.