T-cell receptor on CD4+ αβ T cells specific for Inhibigen peptide–MHC class II (Inhibigen-specific TCR)

The T-cell receptor (TCR) on CD4+ αβ T cells specific for the Inhibigen peptide–MHC class II complex is a specialized immune receptor that recognizes a unique inhibitory peptide derived from the Mycobacterium tuberculosis (Mtb) lipoprotein LprG (Rv1411c). The Inhibigen peptide, specifically the 141-155 amino acid sequence (ADAVEDVLTGAVVPT), is presented by Major Histocompatibility Complex (MHC) class II molecules on the surface of antigen-presenting cells. Recognition of this complex by specific TCRs is associated with the inhibition of MHC II antigen processing and the suppression of T-cell responses to other mycobacterial antigens, a key mechanism of immune evasion by M. tuberculosis (Pecora et al., 2006, Journal of Immunology). This TCR-peptide-MHC interaction is a significant target in infectious disease research, where blocking the inhibitory signal could enhance host immunity. Additionally, the Inhibigen peptide is being investigated for its potential to induce immune tolerance, making this TCR a target of interest for treating autoimmune and inflammatory conditions by harnessing its natural suppressive properties. The interaction between the TCR and the Inhibigen-MHC II complex initiates a signaling cascade that can lead to the expansion of regulatory-like T cells or the induction of anergy in effector T cells. Understanding the structural basis of this recognition is crucial for developing drugs that can either disrupt this evasion tactic or utilize it for therapeutic immunosuppression.

Other names

LprG(141-155)-specific T-cell receptorRv1411c(141-155)-specific TCRInhibigen-MHC II specific TCRInhibigen-specific T-cell receptor

The TCR recognizes the Inhibigen peptide (derived from M. tuberculosis LprG) presented by MHC class II molecules. This interaction initiates a signaling cascade that inhibits the processing and presentation of other antigens and promotes an immunosuppressive or regulatory T-cell phenotype, facilitating pathogen persistence.