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

Identification of apoB-100 Peptide-Specific CD8+ T Cells in Atherosclerosis.
Author Information (click to view)

Dimayuga PC, Zhao X, Yano J, Lio WM, Zhou J, Mihailovic PM, Cercek B, Shah PK, Chyu KY,


Dimayuga PC, Zhao X, Yano J, Lio WM, Zhou J, Mihailovic PM, Cercek B, Shah PK, Chyu KY, (click to view)

Dimayuga PC, Zhao X, Yano J, Lio WM, Zhou J, Mihailovic PM, Cercek B, Shah PK, Chyu KY,

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Journal of the American Heart Association 2017 07 156(7) pii e005318
Abstract
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.

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