title: A deficient translocation of CD3ζ, ZAP-70 and Grb2 to lipid raft, as a hallmark of defective adaptive immune response during chronic hepatitis B infection.
abstract: Hepatitis B is considered to be a worldwide public health problem. An immunosuppressor microenvironment has been proposed to contribute to viral persistence during chronic disease. Understanding the intracellular signaling cascade in T-cells from HBV-infected patients, will contribute to unravel the mechanisms that control the development of immune response during hepatitis B. We analyze lipid rafts formation and early activation signals in chronic HBV infected patients, compared to naturally immune subjects (NIS). Patients show: (1) diminished GM1 clustering, (2) A deficient lipid rafts recruitment of CD3ζ/ZAP-70/Grb2, and (3) these proteins do not merge with GM1 within the lipid rafts. Finally, immunoprecipitation assays proved that ZAP-70 does not associate to CD3ζ. These results show for the first time, defects regarding early key events in T-cell activation, in chronically infected HBV patients, which may contribute not only to understand HBV immune tolerance, but to reveal new potential therapeutic targets to control the infection.
authors.affiliation: Institute of Clinical Immunology, University of Los Andes, Merida, Venezuela.
authors.forename: Luisa
authors.initials: L
authors.lastname: Barboza
authors.forename: Siham
authors.initials: S
authors.lastname: Salmen
authors.forename: Guillermo
authors.initials: G
authors.lastname: Teran-Angel
authors.forename: Darrell L
authors.initials: DL
authors.lastname: Peterson
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Berrueta
mesh_terms: D056704:Adaptive Immunity; D017252:CD3 Complex / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D051380:GRB2 Adaptor Protein / Q000276:immunology* / Q000378:metabolism; D006515:Hepatitis B virus / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D021962:Membrane Microdomains / Q000276:immunology* / Q000378:metabolism; D008856:Microscopy, Fluorescence; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D049128:Sphingolipid Activator Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000276:immunology* / Q000378:metabolism
chemical_list: D017252:CD3 Complex; C121704:CD3 antigen, zeta chain; D051380:GRB2 Adaptor Protein; D012367:RNA, Viral; D049128:Sphingolipid Activator Proteins; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human
keywords: Cell signaling; Hepatitis B; Lipid rafts; Signalosome; T cell