T cell receptor–major histocompatibility complex complex (TCR–MHC complex)

The T cell receptor–major histocompatibility complex complex (TCR–MHC complex) is a pivotal molecular assembly in adaptive immunity, resulting from the direct interaction between the T cell receptor (TCR) on T lymphocytes and a peptide-bound major histocompatibility complex (MHC) molecule on antigen-presenting cells[1][2][3][7]. The TCR is a membrane-bound heterodimer, most commonly of α and β chains, recognizing specific peptides presented by highly polymorphic class I or class II MHC proteins, which themselves bind processed antigenic fragments and display them on the cell surface. This interaction triggers intracellular signaling in the T cell, leading to its activation—proliferation, cytokine secretion, and differentiation into effector subtypes[2][6][7]. The specificity of this recognition is both peptide- and MHC allele-dependent, a concept termed "MHC restriction"[1][5]. This complex is central to immune responses against infection and cancer, as well as to immune tolerance and the pathogenesis of autoimmunity and transplant rejection[1][6]. Therapeutic manipulation of TCR–MHC signaling is the basis for many modern immunotherapies, but also carries risks such as excessive immune activation and autoimmunity due to the fundamental role of this complex in immune regulation[6][7].

Other names

TCR–MHCT cell receptor–MHC complexTCR:pMHC complexTCR–peptide–MHC complexT cell receptor–peptide–major histocompatibility complex

Blockade or modulation of TCR signaling (checkpoint inhibitors) Redirected lysis via TCR-pMHC interaction (bispecific antibodies, CAR-T cells) Enhancement or suppression of T cell activation Induction of immune tolerance