T-cell receptor recognizing peptide-HLA-A2 complex (TCR-pHLA-A2)

The T-cell receptor (TCR) recognizing peptide-HLA-A2 complexes is a fundamental component of the adaptive immune system, responsible for identifying intracellular antigens presented on the cell surface. HLA-A2, specifically the HLA-A*02:01 allele, is one of the most prevalent human leukocyte antigen (HLA) types in many populations, making it a primary focus for MHC-restricted immunotherapies (Gonzalez-Galarza et al., 2020). The TCR specifically binds to a complex formed by the HLA-A2 molecule and a short peptide fragment (typically 8-11 amino acids) derived from cellular proteins (Rossjohn et al., 2015). In oncology, this interaction is exploited by engineering T cells with specific TCRs or using bispecific molecules like ImmTACs to target tumor-associated antigens such as NY-ESO-1, MAGE-A4, or gp100. For instance, Tebentafusp is a bispecific protein that redirects T cells to kill gp100-positive melanoma cells in HLA-A*02:01-positive patients (Nathan et al., 2021). Similarly, Afamitresgene autoleucel is an adoptive cell therapy targeting MAGE-A4 in synovial sarcoma (D'Angelo et al., 2024). While highly effective, these therapies require precise specificity to avoid lethal cross-reactivity with similar peptides in healthy tissues and are associated with risks like cytokine release syndrome.

Other names

TCR-pMHC complexHLA-A*02:01-peptide-TCR complexMHC-restricted T-cell receptorT-cell receptor-MHC-peptide complex

T-cell redirection and activation via specific recognition of peptide-MHC complexes, often through engineered TCRs (TCR-T) or bispecific TCR-anti-CD3 fusion proteins (ImmTACs).