T-cell receptor-Major Histocompatibility Complex (TCR-MHC) interaction (TCR-MHC)

The interaction between T-cell receptors (TCRs) and Major Histocompatibility Complex (MHC) class I and II molecules on dendritic cells (DCs) constitutes the fundamental unit of the adaptive immune response, often referred to as the immunological synapse (Janeway's Immunobiology). Dendritic cells act as professional antigen-presenting cells that process pathogens or tumor-derived proteins into peptides, which are then displayed on MHC molecules (StatPearls). MHC class I molecules present endogenous antigens to CD8+ cytotoxic T-cells, while MHC class II molecules present exogenous antigens to CD4+ helper T-cells (NIH). The TCR specifically recognizes the peptide-MHC (pMHC) complex, initiating a signaling cascade that leads to T-cell proliferation and effector function (UniProt). In cancer, this interaction is often subverted by tumor-induced immunosuppression, making it a primary target for immunotherapies such as TCR-engineered T-cells (e.g., Afamitresgene autoleucel) and bispecific TCR molecules (e.g., Tebentafusp) (FDA). Conversely, in autoimmune diseases, the inappropriate recognition of self-peptides by TCRs leads to tissue destruction, which drugs like Abatacept aim to modulate by interfering with co-stimulatory signals (PubMed). Therapeutic challenges include the risk of cytokine release syndrome (CRS) and 'on-target, off-tumor' toxicities if the targeted peptide is expressed in healthy tissues (Nature Reviews Drug Discovery).

Other names

Immunological synapseAntigen presentation complexTCR-pMHC complexMHC-TCR axis

Modulation of T-cell activation through the recognition of peptide-MHC complexes by T-cell receptors.