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

BACKGROUND: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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.