Heat shock protein 70-mediated immune receptors (HSP70 receptors)

Heat shock protein 70 (HSP70)-mediated immune receptors are a functional group of cell surface proteins that recognize extracellular HSP70, which acts as a damage-associated molecular pattern (DAMP). This group includes diverse receptors such as CD91 (LRP1), LOX-1, SREC-I, and Toll-like receptors 2 and 4 (TLR2/4), which are primarily expressed on professional antigen-presenting cells like dendritic cells and macrophages (Binder et al., Nature Medicine 2000; Asea et al., Nature Medicine 2000). When HSP70 is released from stressed or necrotic cells, it often carries tumor-derived or pathogen-derived peptides; the binding of these complexes to HSP70 receptors facilitates the internalization and cross-presentation of the peptides to CD8+ T cells, thereby initiating a specific cellular immune response (Delneste et al., Immunity 2002). In oncology, these receptors are the primary targets for autologous HSP-based vaccines, such as Vitespen, which leverage the natural adjuvant properties of HSP70 to enhance anti-tumor immunity (ClinicalTrials.gov). However, chronic activation of these receptor pathways by extracellular HSP70 is also associated with the pathogenesis of inflammatory and autoimmune diseases, making them targets for immunomodulatory therapies.

Other names

HSP70-binding receptorsExtracellular HSP70 receptorsCD91Low-density lipoprotein receptor-related protein 1 (LRP1)Lectin-like oxidized LDL receptor-1 (LOX-1)Scavenger receptor expressed on endothelial cells I (SREC-I)Toll-like receptor 2 (TLR2)Toll-like receptor 4 (TLR4)CD40

Binding of extracellular Heat shock protein 70 (HSP70) or HSP70-peptide complexes to surface receptors on antigen-presenting cells (APCs) to trigger endocytosis, cross-presentation of chaperoned peptides on MHC class I molecules, and pro-inflammatory signaling via NF-kappaB pathways.