Your browser doesn't support javascript.
loading
Posttranslationally modified self-peptides promote hypertension in mouse models.
Bloodworth, Nathaniel; Chen, Wei; Hunter, Kuniko; Patrick, David; Palubinsky, Amy; Phillips, Elizabeth; Roeth, Daniel; Kalkum, Markus; Mallal, Simon; Davies, Sean; Ao, Mingfang; Moretti, Rocco; Meiler, Jens; Harrison, David G.
Afiliación
  • Bloodworth N; Division of Clinical Pharmacology, Department of Medicine.
  • Chen W; Division of Clinical Pharmacology, Department of Medicine.
  • Hunter K; Division of Clinical Pharmacology, Department of Medicine.
  • Patrick D; Division of Clinical Pharmacology, Department of Medicine.
  • Palubinsky A; Department of Medicine, and.
  • Phillips E; Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
  • Roeth D; Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Australia.
  • Kalkum M; Center for Drug Safety and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
  • Mallal S; Department of Immunology and Theranostics, Beckman Research Institute, City of Hope, Duarte, California, USA.
  • Davies S; Department of Immunology and Theranostics, Beckman Research Institute, City of Hope, Duarte, California, USA.
  • Ao M; Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
  • Moretti R; Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Australia.
  • Meiler J; Division of Clinical Pharmacology, Department of Medicine.
  • Harrison DG; Division of Clinical Pharmacology, Department of Medicine.
J Clin Invest ; 134(16)2024 Aug 15.
Article en En | MEDLINE | ID: mdl-39145457
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.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Procesamiento Proteico-Postraduccional / Modelos Animales de Enfermedad / Hipertensión Límite: Animals / Humans Idioma: En Revista: J Clin Invest Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Procesamiento Proteico-Postraduccional / Modelos Animales de Enfermedad / Hipertensión Límite: Animals / Humans Idioma: En Revista: J Clin Invest Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos