@article{6dbe4b91ae93488c8f429b854d2f9af5,
title = "Pleiotropic consequences of metabolic stress for the major histocompatibility complex class II molecule antigen processing and presentation machinery",
abstract = "Hyperglycemia and hyperlipidemia are often observed in individuals with type II diabetes (T2D) and related mouse models. One dysmetabolic biochemical consequence is the non-enzymatic reaction between sugars, lipids, and proteins, favoring protein glycation, glycoxidation, and lipoxidation. Here, we identified oxidative alterations in key components of the major histocompatibility complex (MHC) class II molecule antigen processing and presentation machinery in vivo under conditions of hyperglycemia-induced metabolic stress. These modifications were linked to epitope-specific changes in endosomal processing efficiency, MHC class II-peptide binding, and DM editing activity. Moreover, we observed some quantitative and qualitative changes in the MHC class II immunopeptidome of Ob/Ob mice on a high-fat diet compared with controls, including changes in the presentation of an apolipoprotein B100 peptide associated previously with T2D and metabolic syndrome-related clinical complications. These findings highlight a link between glycation reactions and altered MHC class II antigen presentation that may contribute to T2D complications.",
keywords = "CD4 T cells, MHC class II, advanced glycation end products, antigen processing and presentation, dendritic cells, diabetes, hyperinsulinemia, obesity, oxidative posttranslational modifications",
author = "Clement, {Cristina C.} and Nanaware, {Padma P.} and Takahiro Yamazaki and Negroni, {Maria Pia} and Karthik Ramesh and Kateryna Morozova and Sangeetha Thangaswamy and Austin Graves and Kim, {Hei Jung} and Li, {Tsai Wanxia} and Marco Vigano and Soni, {Rajesh K.} and Massimo Gadina and Tse, {Harley Y.} and Lorenzo Galluzzi and Roche, {Paul A.} and Denzin, {Lisa K.} and Stern, {Lawrence J.} and Laura Santambrogio",
note = "Funding Information: The work was supported by NIH AI146180 and NIH AI137198 (to L.S. and L.J.S.), PHS R01AI117535, The Barile Children's Medical Research Trust and the Robert Wood Johnson Foundation (67038 to the Child Health Institute of New Jersey) (to L.K.D.), and the Intramural Research Program of the National Institutes of Health (to P.A.R.). C.C.C. performed the experiments and wrote the manuscript; P.P.N. T.Y. M.P.N. K.R. K.M. S.T. A.G. H.J.K. T.W.L. M.V. and H.T. performed the experiments; R.S. run all the proteomic analysis and performed the APO-B quantification; M.G. L.G. P.R. L.K.D. L.J.S. and L.S. analyzed the data and wrote the manuscript. The authors declare no competing interests. We worked to ensure sex balance in the selection of non-human subjects. The author list of this paper includes contributors from the location where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work. Funding Information: The work was supported by NIH AI146180 and NIH AI137198 (to L.S. and L.J.S.), PHS R01AI117535 , The Barile Children{\textquoteright}s Medical Research Trust and the Robert Wood Johnson Foundation ( 67038 to the Child Health Institute of New Jersey) (to L.K.D.), and the Intramural Research Program of the National Institutes of Health (to P.A.R.). Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",
year = "2021",
month = apr,
day = "13",
doi = "10.1016/j.immuni.2021.02.019",
language = "English (US)",
volume = "54",
pages = "721--736.e10",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "4",
}
