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

The peptide–major histocompatibility complex–T cell receptor interface is the fundamental molecular recognition surface at which T lymphocytes sense antigenic peptides presented by major histocompatibility complex molecules on the surface of antigen-presenting cells. TCRs scan pMHC molecules with high specificity: TCR engagement induces conformational changes and initiates intracellular kinase cascades leading to T cell activation, clonal expansion, and immune response. This interface is central to adaptive immunity, with its malfunction implicated in infection control failure, autoimmunity, and transplant rejection. Therapeutically, while not a discrete single molecule, this interface is targeted either indirectly (e.g., through anti-CD3 therapy) or as the context for engineered immune cell therapies (such as CAR-T and bispecific antibodies)[1][3][6]. Note: The correct approach for structured information is to select either T cell receptor (TCR; "T cell receptor alpha/beta complex") or specific major histocompatibility complex molecules as the canonical molecular target, not the process/interface. The term as given is thus not a canonical therapeutic target itself.

Other names

TCR-pMHC interactionT cell receptor–peptide–MHC complex interfaceTCR–antigen recognition interfaceTCR–MHC interface

Selective activation or inhibition of T cell signaling by targeting TCR or associated proteins Modulation of immune synapse formation Blocking or mimicking antigenic peptide presentation