CD4+ T-cell receptor recognizing Heat Shock Protein 60 epitope–HLA class II complexes (HSP60-specific TCR)

The CD4+ T-cell receptor (TCR) recognizing Heat Shock Protein 60 (HSP60) epitopes presented by HLA class II molecules is a specialized immune receptor involved in the recognition of cellular stress signals and self-antigens (van Eden et al., 2005 [Nature Reviews Immunology]). HSP60 is a highly conserved molecular chaperone that, under conditions of stress or inflammation, can be expressed on the cell surface or secreted, acting as a potent autoantigen in diseases such as Type 1 Diabetes, Rheumatoid Arthritis, and atherosclerosis (Wick et al., 2004 [Annual Review of Immunology]). These specific TCRs are the primary targets for antigen-specific immunotherapies designed to modulate the immune response. Drugs like DiaPep277, a synthetic peptide derived from HSP60, interact with these TCRs to induce immune tolerance by shifting the cytokine profile from a pro-inflammatory Th1 response to a protective regulatory T-cell (Treg) or Th2-mediated response (Raz et al., 2001 [The Lancet]). This therapeutic approach aims to arrest the autoimmune destruction of tissues, such as pancreatic beta cells, while avoiding the risks of systemic immunosuppression (Huurman et al., 2008 [Diabetes]). However, the efficacy of targeting these receptors is often dependent on the patient's HLA genotype, presenting a challenge for broad clinical application.

Other names

Heat shock protein 60-reactive T-cell receptorHSP60-specific TCRT-cell receptor recognizing HSP60/MHC-II complexHSP60-reactive CD4+ T-cell receptor

Antigen-specific immunotherapy through the induction of immune tolerance and regulatory T-cell (Treg) differentiation.