AUTHOR=Shaw Michael K. , Tse Kevin Y. , Zhao Xiaoqing , Welch Kathryn , Eitzman Daniel T. , Thipparthi Raghavendar R. , Montgomery Paul C. , Thummel Ryan , Tse Harley Y. 

TITLE=T-Cells Specific for a Self-Peptide of ApoB-100 Exacerbate Aortic Atheroma in Murine Atherosclerosis

JOURNAL=Frontiers in Immunology

VOLUME=Volume 8 - 2017

YEAR=2017

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2017.00095

DOI=10.3389/fimmu.2017.00095

ISSN=1664-3224

ABSTRACT=On the basis of mouse I-Ab binding motifs, two sequences of the murine apolipoprotein ApoB-100, mApoB1003501-3515 (designated P3) and mApoB-100978-992 (designated P6), were found to be immunogenic.  In this report, we show that P6 is also atherogenic. Immunization of Apoe–/– mice fed a high fat diet with P6 resulted in enhanced development of aortic atheroma as compared to control mice immunized with an irrelevant peptide MOG35-55 or with complete Freund's adjuvant (CFA) alone. Adoptive transfer of lymph node cells from P6-immunized donor mice to recipients fed a high fat diet caused exacerbated aortic atheromas, correlating P6-primed cells to disease development. Finally, P6-specific T cell clones were generated and adoptive transfer of T cell clones into recipients fed a high fat diet 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 a high fat diet, 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.