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RESEARCH ARTICLE

Heat shock proteins and immunity: Application of hyperthermia for immunomodulation

, MD, PhD, &
Pages 610-616 | Received 21 Mar 2009, Accepted 07 Sep 2009, Published online: 18 Dec 2009

Figures & data

Figure 1. The role of intracellular HSPs in MHC class I antigen presentation. Cellular proteins are degraded by proteasomes, resulting in production of antigenic peptides. The peptides are transported from the cytosol into the endoplasmic reticulum (ER) by transporters associated with antigen processing (TAP), followed by binding to MHC class I molecules and presentation on the cell surface. Molecular chaperone HSPs are associated with antigenic peptides, proteasomes, TAP and MHC class I in this pathway.

Figure 1. The role of intracellular HSPs in MHC class I antigen presentation. Cellular proteins are degraded by proteasomes, resulting in production of antigenic peptides. The peptides are transported from the cytosol into the endoplasmic reticulum (ER) by transporters associated with antigen processing (TAP), followed by binding to MHC class I molecules and presentation on the cell surface. Molecular chaperone HSPs are associated with antigenic peptides, proteasomes, TAP and MHC class I in this pathway.

Figure 2. The role of extracellular HSPs in immune responses. Extracellular HSPs can stimulate Toll-like receptors, leading to activation of dendritic cells and release of cytokines such as IL-12, TNF-α and interferon (innate immune responses). Extracellular HSPs can be internalised through HSP receptors with HSP-bound peptides. The antigenic peptides are then cross-presented to MHC class I molecules, leading to induction of peptide-specific CTL responses (adaptive immune responses).

Figure 2. The role of extracellular HSPs in immune responses. Extracellular HSPs can stimulate Toll-like receptors, leading to activation of dendritic cells and release of cytokines such as IL-12, TNF-α and interferon (innate immune responses). Extracellular HSPs can be internalised through HSP receptors with HSP-bound peptides. The antigenic peptides are then cross-presented to MHC class I molecules, leading to induction of peptide-specific CTL responses (adaptive immune responses).

Figure 3. Cross-presentation pathway of Hsp90-antigen complex. HSP-antigen complexes internalised through HSP receptors are transported into the early endosome, followed by processing and presentation through MHC class I in the recycling endosome. Some of the HSP-antigen complexes may be released into the cytosol, followed by transportation through TAP and presentation through MHC class I in the ER.

Figure 3. Cross-presentation pathway of Hsp90-antigen complex. HSP-antigen complexes internalised through HSP receptors are transported into the early endosome, followed by processing and presentation through MHC class I in the recycling endosome. Some of the HSP-antigen complexes may be released into the cytosol, followed by transportation through TAP and presentation through MHC class I in the ER.

Figure 4. Hsp90-peptide vaccine can induce an efficient specific CTL response. HLA-A*2402/Kb-transgenic mice were immunised four times with the indicated peptide vaccination. Spleen cells were removed one week after the last immunisation, cultured for five days with survivin-2B80–88 peptides, and tested for cytotoxicity. Each line represents the specific lysis of target cells by spleen cells from one individual mouse. Target cells were RMA-S/A*2402 cells pulsed with the survivin-2B80–88 peptide, or without the peptide. Note that CTL were induced in the cases of vaccination with Hsp90 + peptide and complete Freund adjuvant (CFA) + peptide. IFA: incomplete Freund adjuvant. (Figure from reference Citation[38]). Copyright 2007. The American Association of Immunologists, Inc.

Figure 4. Hsp90-peptide vaccine can induce an efficient specific CTL response. HLA-A*2402/Kb-transgenic mice were immunised four times with the indicated peptide vaccination. Spleen cells were removed one week after the last immunisation, cultured for five days with survivin-2B80–88 peptides, and tested for cytotoxicity. Each line represents the specific lysis of target cells by spleen cells from one individual mouse. Target cells were RMA-S/A*2402 cells pulsed with the survivin-2B80–88 peptide, or without the peptide. Note that CTL were induced in the cases of vaccination with Hsp90 + peptide and complete Freund adjuvant (CFA) + peptide. IFA: incomplete Freund adjuvant. (Figure from reference Citation[38]). Copyright 2007. The American Association of Immunologists, Inc.

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