Human T-cell receptor–Major Histocompatibility Complex–coronavirus epitope complex (TCR–pMHC–CoV complex)

The Human T-cell receptor–Major Histocompatibility Complex–coronavirus epitope complex is a fundamental molecular assembly required for the adaptive immune system to identify and eliminate coronavirus-infected cells (Nguyen et al., 2021, Nature Reviews Immunology). This complex forms when a T-cell receptor (TCR) on the surface of a T lymphocyte binds to a specific viral peptide fragment (epitope) presented by a Major Histocompatibility Complex (MHC) molecule, such as HLA-A*02:01 (Wu et al., 2022, Nature Communications). The formation of this tripartite structure triggers T-cell activation, leading to the release of cytotoxic granules and pro-inflammatory cytokines like interferon-gamma to control the infection (Sette & Crotty, 2021, Cell). In the context of COVID-19, these complexes are the primary targets for vaccine-induced T-cell responses and are being explored for TCR-engineered T-cell therapies (TCR-T) to treat severe or persistent infections (Pan et al., 2021, Science Immunology). Therapeutic strategies aim to either induce the formation of these complexes through vaccination or utilize synthetic receptors to mimic this natural recognition process. However, challenges include the high polymorphism of human HLA genes, which limits the broad applicability of specific TCR-based treatments, and the risk of viral variants escaping recognition through mutations in key epitopes (Altmann & Boyton, 2021, Science).

Other names

TCR-pMHC complexHLA-peptide-TCR complexSARS-CoV-2 TCR-pMHC complexT-cell receptor–antigen–MHC complexpMHC-TCR complex

The complex facilitates the recognition of viral antigens by T-cells, triggering intracellular signaling pathways that lead to T-cell proliferation, cytokine production, and direct lysis of infected cells.