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The role of heat shock proteins in antigen cross presentation - PubMed

  • ️Sun Jan 01 2012

The role of heat shock proteins in antigen cross presentation

Ayesha Murshid et al. Front Immunol. 2012.

Abstract

Heat shock proteins (HSPs) are molecular chaperones that bind tumor antigens and mediate their uptake into antigen presenting cells. HSP-antigen complexes are then directed toward either the MHC class I pathway through antigen cross presentation or the conventional class II pathway, leading to activation of T cell subsets. Uptake of HSP-chaperoned polypeptides can involve both receptor-mediated and receptor-independent routes, and mechanisms of antigen sorting between the Class I and II pathways after uptake are currently under investigation. The processes involved in internalization of HSP-antigen complexes differ somewhat from the mechanisms previously determined for (unchaperoned) particulate and free soluble antigens. A number of studies show that HSP-facilitated antigen cross presentation requires uptake of the complexes by scavenger receptors (SR) followed by processing in the proteasome, and loading onto MHC class I molecules. In this review we have examined the roles of HSPs and SR in antigen uptake, sorting, processing, cell signaling, and activation of innate and adaptive immunity.

Keywords: CTL response; anti-cancer vaccine; antigen cross presentation; antigen presenting cells; heat shock proteins; scavenger receptor; soluble vs. particulate antigen; tumor immunity.

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Figures

Figure 1
Figure 1

Antigen presentation pathways for HSP-bound polypeptides. HSP.PCs bind to surface receptors on DC including SRECI and LOX-1 and are internalized in complexes with the receptors. Binding to these receptors may also trigger secondary activation of Toll-like receptors (TLR2 or TLR4) that may amplify antigen cross presentation. Alternatively some studies suggest direct binding of HSPs to TLR. HSP binding to cell surface SRA/CD204 is inhibitory to TLR4 activity and likely antagonizes the immune responses induced by HSPs through LOX-1 or SRECI. HSP.PC are internalized by SRECI or LOX-1 into endosomes with the subsequent release of the peptides from the HSP.PC complex. Such peptides are then processed either within endosomes or undergo trafficking to the cytosol where they encounter the proteasomal system. Processed peptides are then loaded either onto MHC class I in the ER or phagosomes or onto MHC class II molecules in lysosomes and presented to, respectively CD8+ T cells and CD4+ T cells. The triage mechanisms directing HSP-chaperoned peptides toward either of these two pathways are currently not known.

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