摘要：SummaryAdaptive 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.Graphical AbstractDisplay OmittedHighlights•Obesity reshapes the landscape of VAT-derived MIP•The obese VAT-exclusive MIP reflects an obesity-associated signature•An obese VAT-exclusive peptide LDHA237-244can stimulate CD8+T cell responses•LDHA237-244-reactive CD8+T cells were present in obese mice but not lean miceDiabetology; Immunology; Proteomics
