Target intelligence / Profile preview

T-cell receptor on HSP70-B29-specific CD4+ T cells (TCR (HSP70-B29))

Target
TCR (HSP70-B29)
Molecular classification
Receptor, T-cell receptor complex, Antigen-specific receptor
01

Overview

The T-cell receptor (TCR) on HSP70-B29-specific CD4+ T cells is a specialized immune receptor that recognizes the B29 peptide, a highly conserved sequence (VLDVPLTAD) derived from the 70 kDa heat shock protein (HSP70). This TCR-peptide interaction is a key focus in the development of tolerogenic therapies for autoimmune diseases, particularly rheumatoid arthritis. When the B29 peptide is presented by MHC class II molecules, it binds to this specific TCR, triggering the activation and expansion of regulatory T cells (Tregs). These activated Tregs migrate to sites of inflammation and suppress pathogenic immune responses through the secretion of anti-inflammatory cytokines such as IL-10. (Wieten, L., et al., 2010, Science Translational Medicine; van Eden, W., et al., 2012, Nature Reviews Rheumatology). By targeting this TCR with specific peptides or DNA-based vaccines, researchers aim to restore immune tolerance and reduce chronic inflammation without causing systemic immunosuppression. This approach leverages the natural ability of heat shock proteins to act as 'danger signals' that can be modulated to induce a protective, regulatory immune environment. (van Herwijnen, M. J., et al., 2012, Journal of Immunology; Prakken, B. J., et al., 2004, Lancet).

Other names
B29-specific T-cell receptorHSP70 peptide B29-specific TCRHeat shock protein 70 B29-specific T-cell receptor
02

Mechanism of action

Activation of regulatory T cells (Tregs) through TCR recognition of the B29 peptide presented on MHC Class II (HLA-DR) molecules, leading to the secretion of anti-inflammatory cytokines such as IL-10 and TGF-beta to suppress autoimmune inflammation.

03

Biological functions

Immune responseImmune regulationAntigen recognitionT-cell activationInduction of peripheral tolerance
04

Disease associations

Rheumatoid arthritisAutoimmune diseaseInflammationJuvenile idiopathic arthritis
05

Safety considerations

Potential for unintended activation of effector T cells (Th1/Th17) instead of regulatory T cellsCross-reactivity with other self-peptidesRisk of cytokine release syndrome (though low for Treg-inducing therapies)MHC restriction (efficacy may depend on patient HLA type)
06

Interacting drugs

B29 peptide (VLDVPLTAD)

1 more in the full profile.

07

Biomarkers

Interleukin-10 (IL-10) productionCD4+CD25+Foxp3+ T cell frequencyB29-specific T cell proliferationReduction in C-reactive protein (CRP)

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