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Journal article
Posttranslationally modified self-peptides promote hypertension in mouse models
The Journal of Clinical Investigation, Vol.134(16), e174374
2024
Abstract
Posttranslational modifications can enhance immunogenicity of self-proteins. In several conditions, including hypertension, systemic lupus erythematosus, and heart failure, isolevuglandins (IsoLGs) are formed by lipid peroxidation and covalently bond with protein lysine residues. Here, we show that the murine class I major histocompatibility complex (MHC-I) variant H-2Db uniquely presents isoLG-modified peptides and developed a computational pipeline that identifies structural features for MHC-I accommodation of such peptides. We identified isoLG-adducted peptides from renal proteins, including sodium glucose transporter 2, cadherin 16, Kelch domain–containing protein 7A, and solute carrier family 23, that are recognized by CD8+ T cells in tissues of hypertensive mice, induce T cell proliferation in vitro, and prime hypertension after adoptive transfer. Finally, we find patterns of isoLG-adducted antigen restriction in class I human leukocyte antigens that are similar to those in murine analogs. Thus, we have used a combined computational and experimental approach to define likely antigenic peptides in hypertension.
Details
- Title
- Posttranslationally modified self-peptides promote hypertension in mouse models
- Authors/Creators
- Nathaniel BloodworthWei ChenKuniko HunterDavid PatrickAmy M. Palubinsky - Vanderbilt University School of MedicineElizabeth PhillipsDaniel RoethMarkus KalkumSimon MallalSean DaviesMingfang AoRocco MorettiJens MeilerDavid G. Harrison
- Publication Details
- The Journal of Clinical Investigation, Vol.134(16), e174374
- Publisher
- American Society for Clinical Investigation
- Identifiers
- 991005695569207891
- Copyright
- © 2024 Bloodworth et al.
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Resource Type
- Journal article
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