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Role of Wnt5A Signaling in Antigen Processing and Presentation

EPrints@IICB

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Field Value
 
Title Role of Wnt5A Signaling in Antigen Processing and Presentation
 
Creator Sarraf, Tresa Rani
 
Subject Cancer Biology and Inflammatory Disorder Division
 
Description The adaptive immune system relies on the efficient processing of exogenous antigens and the cross-presentation of antigen to T cells. Dendritic cells are potent antigen-presenting cells, which have the ability to cross-present antigens and promote the generation of antigen-specific CD8 T cell response. Yet several questions remain unresolved in dendritic cell-mediated antigen cross-presentation. One of the very important questions in this field is how dendritic cells regulate the supply of exogenous antigens to the conventional exogenous pathways or cross-presentation pathways. The host factors that decide and modulate the cross-presentation of exogenous antigens are still unknown. In this study, I demonstrated that host protein Wnt5A, as an immune modulator, promotes cross-presentation in both in-vitro and in-vivo systems. Using mouse bone marrow-derived dendritic cells (BMDC) as antigen-presenting cells and ovalbumin (OVA/DQ-OVA) as a model antigen, I demonstrated that recombinant Wnt5A treatment promotes DQ-OVA processing in BMDC in combination with actin dynamics. Recombinant Wnt5A facilitated DQ-OVA processing depends on proteasome and is compromised by proteasome inhibitor MG132. Mechanistically I demonstrated that Wnt5A depletion leads to reduced DQ-OVA processing and is accompanied by the lower association of actin and proteasome 11S subunit with processed DQ-OVA. Further, I showed that the Wnt5A-actin-proteasome axis directs the antigen cross-presentation and subsequent activation of CD8 T cells. Reduction of Wnt5A results in compromised CD8 T cell activation. Using Wnt5A wild type and heterozygous mice I demonstrated that reduced levels of Wnt5A protein in heterozygous mice led to impaired CD8 T cell activation in presence of ovalbumin. Overall my results proved that Wnt5A signaling is the prerequisite for antigen processing and cross-presentation, thus unveiling a new field in the therapeutic vaccine.
 
Date 2022
 
Type Thesis
NonPeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/2862/1/Thesis_for_evaluation.pdf
Sarraf, Tresa Rani (2022) Role of Wnt5A Signaling in Antigen Processing and Presentation. PhD thesis, UNIVERSITY OF CALCUTTA.
 
Relation http://www.eprints.iicb.res.in/2862/