A deficient translocation of CD3 ζ, ZAP-70 and Grb2 to lipid raft, as a hallmark of defective adaptive immune response during chronic Hepatitis B infection
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1
University of Los Andes, Venezuela
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2
Virginia Commonwealth University, Department of Biochemistry and Molecular Biology, United States
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 chronically 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 CD3 ζ. 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.
Acknowledgements
This work was supported in part by two grants from FONACIT G-2005000407 and CDCHT-ULA M-996-10-07-A.
Keywords:
Hepatitis B,
T cell,
signalosome,
lipid raft,
Cell signaling
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Host-pathogen interactions
Citation:
Barboza
LE,
Salmen
S,
Terán-Angel
G,
Peterson
D and
Berrueta
L
(2013). A deficient translocation of CD3 ζ, ZAP-70 and Grb2 to lipid raft, as a hallmark of defective adaptive immune response during chronic Hepatitis B infection
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Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00402
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Received:
01 Apr 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Luisa E Barboza, University of Los Andes, Mérida, Venezuela, barbozale@gmail.com