Abstract
Introduction Antigen presentation to T cells by dendritic cells is an essential response for the initiation of acquired immunity to eliminate pathogens that have invaded. The pathogen-derived antigens incorporated by dendritic cells are processed into peptides and presented by MHC molecules. There are also mechanisms by which cytoplasmic antigens are presented by MHC molecules. However, it has not been recognized how the HSP family involves antigen presentation. In here, we summarize the current knowledge about the roles of HSP family proteins in antigen presentation.
Methods We review; (i) mechanisms of antigen presentation by dendritic cells, (ii) roles of HSP in antigen presentation by MHC-I, and (iii) roles of HSP in antigen presentation by MHC-II.
Results Recently, the involvement of the HSP family has been revealed at several steps in the process of antigen presentation. In particular, the functions of HSP90 in the MHC-I pathway and the functions of HSP70 in the MHC-II pathway are being elucidated. However, several unsolved questions have still remained. For example, does the same mechanism function in all antigen-presenting cells? Is there specificity for antigen proteins in the HSPs? In addition, the involvement of the other HSPs in antigen presentation is still unclear.
Conclusions Since acquired immunity is important for the elimination of pathogens and tumors, antigen presentation should be a promising target for immunotherapy for infectious diseases and cancers. HSPs may be a potential target for manipulation of antigen presentation.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Abbreviations
- CMA:
-
chaperon-mediated autophagy
- CTL:
-
cytotoxic T lymphocyte
- DC:
-
dendritic cell
- ER:
-
endoplasmic reticulum
- MHC:
-
major histocompatibility complex
- MIIC:
-
MHC-II compartment
- TAP:
-
Transporter associated with antigen processing
References
Binder RJ, Blachere NE, Srivastava PK (2001) Heat shock protein-chaperoned peptides but not free peptides introduced into the cytosol are presented efficiently by major histocompatibility complex I molecules. J Biol Chem 276:17163–17171
Blander JM (2018) Regulation of the cell biology of antigen cross-presentation. Annu Rev Immunol 36:717–753
Cresswell P, Ackerman AL, Giodini A, Peaper DR, Wearsch PA (2005) Mechanisms of MHC class I-restricted antigen processing and cross-presentation. Immunol Rev 207:145–157
Deffit SN, Blum JS (2015a) A central role for HSC70 in regulating antigen trafficking and MHC class II presentation. Mol Immunol 68:85–88
Deffit SN, Blum JS (2015b) Macronutrient deprivation modulates antigen trafficking and immune recognition through HSC70 accessibility. J Immunol 194:1446–1453
Duraes FV, Niven J, Dubrot J, Hugues S, Gannage M (2015) Macroautophagy in endogenous processing of self- and pathogen-derived antigens for MHC class II presentation. Front Immunol 6:459
Graner MW (2016) HSP90 and immune modulation in cancer. Adv Cancer Res 129:191–224
Houlihan JL, Metzler JJ, Blum JS (2009) HSP90alpha and HSP90beta isoforms selectively modulate MHC class II antigen presentation in B cells. J Immunol 182:7451–7458
Ichiyanagi T, Imai T, Kajiwara C, Mizukami S, Nakai A, Nakayama T, Udono H (2010) Essential role of endogenous heat shock protein 90 of dendritic cells in antigen cross-presentation. J Immunol 185:2693–2700
Imai T, Kato Y, Kajiwara C, Mizukami S, Ishige I, Ichiyanagi T, Hikida M, Wang JY, Udono H (2011) Heat shock protein 90 (HSP90) contributes to cytosolic translocation of extracellular antigen for cross-presentation by dendritic cells. Proc Natl Acad Sci U S A 108:16363–16368
Joffre OP, Segura E, Savina A, Amigorena S (2012) Cross-presentation by dendritic cells. Nat Rev Immunol 12:557–569
Kaushik S, Cuervo AM (2018) The coming of age of chaperone-mediated autophagy. Nat Rev Mol Cell Biol 19:365–381
Kettern N, Rogon C, Limmer A, Schild H, Hohfeld J (2011) The Hsc/Hsp70 co-chaperone network controls antigen aggregation and presentation during maturation of professional antigen presenting cells. PLoS One 6:e16398
Kurotaki T, Tamura Y, Ueda G, Oura J, Kutomi G, Hirohashi Y, Sahara H, Torigoe T, Hiratsuka H, Sunakawa H et al (2007) Efficient cross-presentation by heat shock protein 90-peptide complex-loaded dendritic cells via an endosomal pathway. J Immunol 179:1803–1813
Munz C (2016) Autophagy beyond intracellular MHC class II antigen presentation. Trends Immunol 37:755–763
Oura J, Tamura Y, Kamiguchi K, Kutomi G, Sahara H, Torigoe T, Himi T, Sato N (2011) Extracellular heat shock protein 90 plays a role in translocating chaperoned antigen from endosome to proteasome for generating antigenic peptide to be cross-presented by dendritic cells. Int Immunol 23:223–237
Roche PA, Furuta K (2015) The ins and outs of MHC class II-mediated antigen processing and presentation. Nat Rev Immunol 15:203–216
Schmid D, Pypaert M, Munz C (2007) Antigen-loading compartments for major histocompatibility complex class II molecules continuously receive input from autophagosomes. Immunity 26:79–92
Tanaka T, Okuya K, Kutomi G, Takaya A, Kajiwara T, Kanaseki T, Tsukahara T, Hirohashi Y, Torigoe T, Hirata K et al (2015) Heat shock protein 90 targets a chaperoned peptide to the static early endosome for efficient cross-presentation by human dendritic cells. Cancer Sci 106:18–24
Udono H (2012) Heat shock protein magic in antigen trafficking within dendritic cells: implications in antigen cross-presentation in immunity. Acta Med Okayama 66:1–6
Zhou D, Li P, Lin Y, Lott JM, Hislop AD, Canaday DH, Brutkiewicz RR, Blum JS (2005) Lamp-2a facilitates MHC class II presentation of cytoplasmic antigens. Immunity 22:571–581
Acknowledgements
We thank Dr. Stuart K. Calderwood, Dr. Kuniaki Okamoto, Dr. Paul Roche and Dr. Satoshi Tanaka for useful discussion and continuous support. This work was supported in part by JSPS KAKENHI, grant numbers 17K08273 (KF), 17K11642 (TE), SUZUKEN memorial foundation (KF, TE), Smoking Research Foundation (KF), and Koyanagi Foundation (KF).
Disclosure of Interests
All authors declare they have no conflict of interest.
Ethical Approval for Studies Involving Humans
This article does not contain any studies with human participants performed by any of the authors.
Ethical Approval for Studies Involving Animals
This article does not contain any studies with animals performed by any of the authors.
Author information
Authors and Affiliations
Corresponding authors
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2020 Springer Nature Switzerland AG
About this chapter
Cite this chapter
Furuta, K., Eguchi, T. (2020). Roles of HSP on Antigen Presentation. In: Asea, A.A.A., Kaur, P. (eds) Heat Shock Proteins in Human Diseases. Heat Shock Proteins, vol 21. Springer, Cham. https://doi.org/10.1007/7515_2020_5
Download citation
DOI: https://doi.org/10.1007/7515_2020_5
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-62288-6
Online ISBN: 978-3-030-62289-3
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)