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Molecular Chaperones in Health and Disease pp 279–304Cite as

Heat Shock Proteins in Immunity

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Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 172))

Abstract

This chapter focuses on immunological effects of eukaryotic and microbial heat shock proteins (HSPs), with molecular weights of about 60, 70, and 90 kDa. The search for tumor-specific antigens resulted in the identification of HSPs. They have been found to elicit a potent anti-cancer immune response mediated by the adoptive and innate immune system. Following receptor-mediated uptake of HSP (HSP70 and gp96) peptide complexes by antigen-presenting cells and representation of HSP-chaperoned peptides byMHC class I molecules, a CD8-specific T cell response is induced.Apart fromchaperoning immunogenic peptides derived fromtumors, bacterial and virally infected cells, they by themselves provide activatory signals for antigen-presenting cells and natural killer (NK) cells. After binding of peptide-free HSP70 to Toll-like receptors, the secretion of pro-inflammatory cytokines is initiated by antigen-presenting cells and thus results in a nonspecific stimulation of the immune system. Moreover, soluble as well as ell membrane-bound HSP70 on tumor cells can directly activate the cytolytic and migratory capacity of NK cells. Apart form cancer, HSPs of different origins, with a molecular weight of about 60, 70, and 90 kDa, also play a pivotal role in viral infections, including human and simian immunodeficiency virus (HIV, SIV), measles, and choriomeningitis. Moreover, HSPs have been found to induce tolerance against autoimmune diseases. In summary, depending on their mode of induction, intracellular/extracellular location, cellular origin (eukaryote/prokaryote), peptide loading status, intracellular ADP/ATP content, concentration, and route of application, HSPs either exert immune activation as danger signals in cancer immunity and mediate protection against infectious diseasesor exhibit regulatory activities in controllingandpreventing autoimmunity.

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  1. Department of Hematology and Oncology, University Hospital Regensburg, Franz-Josef Strauss Allee 11, 93053, Regensburg, Germany

    G. Multhoff

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  1. G. Multhoff
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  1. Freiburg i.

    K. Starke

  2. Medical School Hannover, Carl-Neuberg-Str. 1, 30625, Hannover, Germany

    Matthias Gaestel (Professor) (Professor)

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Multhoff, G. (2006). Heat Shock Proteins in Immunity. In: Starke, K., Gaestel, M. (eds) Molecular Chaperones in Health and Disease. Handbook of Experimental Pharmacology, vol 172. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-29717-0_12

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