title: T-Cells Specific for a Self-Peptide of ApoB-100 Exacerbate Aortic Atheroma in Murine Atherosclerosis.
abstract: On the basis of mouse I-Ab-binding motifs, two sequences of the murine apolipoprotein B-100 (mApoB-100), mApoB-1003501-3515(designated P3) and mApoB-100978-992(designated P6), were found to be immunogenic. In this report, we show that P6 is also atherogenic. Immunization ofApoe-/-mice fed a high-fat diet (HFD) with P6 resulted in enhanced development of aortic atheroma as compared to control mice immunized with an irrelevant peptide MOG35-55or with complete Freund's adjuvant alone. Adoptive transfer of lymph node cells from P6-immunized donor mice to recipients fed an HFD caused exacerbated aortic atheromas, correlating P6-primed cells with disease development. Finally, P6-specific T cell clones were generated and adoptive transfer of T cell clones into recipients fed an HFD led to significant increase in aortic plaque coverage when compared to control animals receiving a MOG35-55-specific T cell line. Recipient mice not fed an HFD, however, did not exhibit such enhancement, indicating that an inflammatory environment facilitated the atherogenic activity of P6-specific T cells. That P6 is identical to or cross-reacts with a naturally processed peptide of ApoB-100 is evidenced by the ability of P6 to stimulate the proliferation of T cells in the lymph node of mice primed by full-length human ApoB-100. By identifying an atherogenic T cell epitope of ApoB-100 and establishing specific T cell clones, our studies open up new and hitherto unavailable avenues to study the nature of atherogenic T cells and their functions in the atherosclerotic disease process.
authors.affiliation: Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, MI, USA; Department of Research and Clinical Trials, St. John-Providence Health System, Macomb-Oakland Hospital, Warren, MI, USA.
authors.forename: Michael K
authors.initials: MK
authors.lastname: Shaw
authors.affiliation: Division of Rheumatology, Allergy and Immunology, Department of Internal Medicine, University of California at San Diego Medical Center, La Jolla, CA, USA; Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
authors.forename: Kevin Y
authors.initials: KY
authors.lastname: Tse
authors.affiliation: Department of Immunology and Microbiology, Wayne State University School of Medicine , Detroit, MI , USA.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Immunology and Microbiology, Wayne State University School of Medicine , Detroit, MI , USA.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Welch
authors.affiliation: Cardiovascular Medicine, University of Michigan Cardiovascular Center , Ann Arbor, MI , USA.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Eitzman
authors.affiliation: Department of Immunology and Microbiology, Wayne State University School of Medicine , Detroit, MI , USA.
authors.forename: Raghavendar R
authors.initials: RR
authors.lastname: Thipparthi
authors.affiliation: Department of Immunology and Microbiology, Wayne State University School of Medicine , Detroit, MI , USA.
authors.forename: Paul C
authors.initials: PC
authors.lastname: Montgomery
authors.affiliation: Department of Anatomy and Cell Biology, Wayne State University School of Medicine , Detroit, MI , USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Thummel
authors.affiliation: Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, MI, USA; Cardiovascular Research Institute, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: Harley Y
authors.initials: HY
authors.lastname: Tse
keywords: T-cell; adoptive transfer; atherosclerosis; clones; epitopes; peptides