Peptide-major histocompatibility complex–T cell receptor interface (pMHC–TCR interface)

The peptide-major histocompatibility complex–T cell receptor interface is the physical region where a T cell receptor docks on a peptide-loaded MHC molecule presented by an antigen-presenting cell. This contact determines the specificity of T cell–mediated immune responses. The interface is composed of structural elements from both the TCR (mainly the variable domains with complementarity-determining regions) and the pMHC (MHC protein α-helices and the presented peptide). Docking is highly conserved in geometry but varies in detail, affecting the strength, specificity, and outcome of T cell activation. The formation of the pMHC–TCR complex is a critical checkpoint for adaptive immune surveillance, self/non-self discrimination, and is central to multiple disease processes including cancer, autoimmune disorders, and infections[1][4][6]. Therapeutic efforts aim to manipulate this interface to enhance, suppress, or redirect T cell function, but present substantial challenges due to the diversity of TCRs, peptides, and MHC alleles involved in human immunity[6][5].

Other names

TCR-pMHC interfaceT cell receptor/peptide-MHC binding interfaceTCR:peptide-MHC interaction surface

Modulate or block antigen recognition by TCR; Redirect TCR specificity (engineered TCRs or CAR-T); Inhibit signaling downstream of TCR–pMHC ligation.