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Investigation and Identification of Novel Heat Shock Protein Hsp70L1 Receptors on Human Dendritic Cells

Author: FangHongLiang
Tutor: WanTao
School: Second Military Medical University
Course: Basic Medical
Keywords: Dendritic cells Adjuvant GST Pull Down Receptor Cloning and Expression TLR4 CD40 Lox-1 TLR2
CLC: R392
Type: Master's thesis
Year: 2009
Downloads: 81
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Abstract

Hsp70L1 from human dendritic cells ( Dendritic cell , DC ) cDNA library discovered a new molecule , with a high degree of homology with members of the HSP70 family . Can the reorganization Hsp70L1 protein induce DC maturation and expression of IL-10p70, MIP-1α, MIP-1β, RANTES, TNF-α and IL -1β and other cytokines and chemokines ; simultaneously with adjuvant -like effect , enhanced antigen-specific cellular immune responses. The purpose of this study is to find and identification the DC surface Hsp70L1 related protein receptor , to elucidate the molecular mechanisms of the research Hsp70L1 receptors play an adjuvant effect the principle . First, we expressed and purified the GST-Hsp70L1 fusion protein , GST Pull-Down technology to find can combine the DC membrane proteins , Western -Blot results show that TLR2, TLR4 and Lox-1 in vitro binding and Hsp70L1 ; based on by receptor expressing clones , clones stably expressing the HSP70 protein family receptor CD40 , CCR5 , LOX - 1 in HEK293 cells expressing strain observed Hsp70L1 protein binding . The results showed TLR4 and CD40 can be combined with Hsp70L1 the CCR5 and LOX-1 is not combined with HSP70L1 ; subsequent study TLR4 and Hsp70L1 protein interaction between the biological effects , the results show that : Hsp70L1 can be induced in wild-type mice , but not able to induce TLR4 - defective mice DC phenotypic changes and inflammatory cytokine TNF-α and IL-1β expression HSP70L1 in wild mice model , but not TLR4 mouse model mediated CEA -specific cellular immune responses enhanced ; using human the load of the inhibitor can inhibit TLR4 HSP70L1 mediated CEA antigen specific cellular immune responses induced by DC . HSP70L1 and TLR4 role in signal transduction studies have shown that the activation of MAPK and NF-κB cascade signaling pathway . TLR4 is Hsp70L1 induce DC maturation phenotypic changes and inflammatory factor expression and induction of specific T cell response in a key functional receptor . These results provides a theoretical basis for Hsp70L1 immunoadjuvant function .

Investigation and Identification of Novel Heat Shock Protein Hsp70L1 Receptors on Human Dendritic Cells

Abstract

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