Obesity Reshapes Visceral Fat-Derived MHC I Associated-Immunopeptidomes and Generates Antigenic Peptides to Drive CD8+ T Cell Responses

• Main Authors: Xiaoling Chen, Shufeng Wang, Yi Huang, Xia Zhao, Xu Jia, Gang Meng, Qian Zheng, Mengjun Zhang, Yuzhang Wu, Li Wang
• Format: Article
• Language: English
• Published: Elsevier 2020-04-01
• Series: iScience
• Online Access: http://www.sciencedirect.com/science/article/pii/S2589004220301619

Summary: Adaptive CD8+ T cells were observed to contribute to the initiation and progression of obesity-induced visceral adipose tissue (VAT) chronic inflammation that is critically linked to metabolic disorders. Numerous peptides presented by the major histocompatibility complex (MHC) class I molecules at the cell surface are collectively termed as MHC I-associated immunopeptidome (MIP) for the interaction with CD8+ T cells. We conducted the in-depth mapping of MIP of VAT from lean and obese mice using large-scale high-resolution mass spectrometry and observed that obesity significantly alters the landscape of VAT MIPs. Additionally, the obese VAT-exclusive MIP source proteome reflected a distinct obesity-associated signature. A peptide derived from lactate dehydrogenase A (LDHA) or B chain, named LDHA237-244, was identified as an obese VAT-exclusive immunogenic peptide that was capable of eliciting pro-inflammatory CD8+ T cells responses. Our findings suggest that certain immunogenic peptides generated by obesity may trigger CD8+ T cell-mediated VAT inflammation. : Diabetology; Immunology; Proteomics Subject Areas: Diabetology, Immunology, Proteomics