Chen Xiaoling, Wang Shufeng, Huang Yi, Zhao Xia, Jia Xu, Meng Gang, Zheng Qian, Zhang Mengjun, Wu Yuzhang, Wang Li
Institute of Immunology PLA, Army Medical University (Third Military Medical University), Chongqing 400038, China.
Biomedical Analysis Center, Army Medical University (Third Military Medical University), Chongqing 400038, China.
iScience. 2020 Apr 24;23(4):100977. doi: 10.1016/j.isci.2020.100977. Epub 2020 Mar 13.
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 LDHA, 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.
研究发现适应性CD8 T细胞会促使肥胖诱导的内脏脂肪组织（VAT）慢性炎症的发生与发展，而这种炎症与代谢紊乱密切相关。细胞表面主要组织相容性复合体（MHC）I类分子呈递的众多肽段统称为MHC I相关免疫肽组（MIP），用于与CD8 T细胞相互作用。我们使用大规模高分辨率质谱对瘦小鼠和肥胖小鼠的VAT的MIP进行了深入分析，发现肥胖显著改变了VAT MIP的格局。此外，肥胖VAT特有的MIP来源蛋白质组反映出一种独特的肥胖相关特征。一种源自乳酸脱氢酶A（LDHA）或B链的肽段，命名为LDHA，被鉴定为肥胖VAT特有的免疫原性肽段，能够引发促炎性CD8 T细胞反应。我们的研究结果表明，肥胖产生的某些免疫原性肽段可能会引发CD8 T细胞介导的VAT炎症。
