T-cell receptor–peptide–major histocompatibility complex (TCR-pMHC) interaction (TCR-pMHC)

The T-cell receptor (TCR) recognition of peptide–major histocompatibility complex (pMHC) is the central event of the adaptive immune system, where a TCR on a T-cell binds to a specific peptide presented by an MHC molecule on a target cell (Rossjohn et al., 2015). In the context of polyclonal recognition, a diverse population of T-cells interacts with various pMHC complexes, a process essential for broad pathogen defense but also the primary driver of graft-versus-host disease (GvHD) in hematopoietic stem cell transplantation (Shlomchik, 2007). This interaction is a major therapeutic target; for instance, immunosuppressants like cyclosporine inhibit the signaling cascade initiated by TCR-pMHC binding, while newer TCR-engineered T-cell therapies (TCR-T) seek to harness this recognition to eliminate tumor cells (June et al., 2018). The specificity and affinity of this recognition determine the potency and safety of the immune response, making it a focal point for drug development in oncology and transplantation (Murphy & Weaver, 2016). Challenges include managing off-target effects where T-cells recognize similar pMHC complexes on healthy tissues, leading to severe toxicity.

Other names

TCR-antigen recognitionMHC-restricted antigen recognitionT-cell synapse formationPolyclonal T-cell recognition

Modulation of T-cell activation by interfering with or enhancing the TCR-pMHC binding or its downstream signaling pathways.