T-cell receptor-peptide-HLA-A*02:01 complex (TCR-pMHC-A*02:01)

The T-cell receptor (TCR) interaction with peptide-HLA-A*02:01 complexes is a fundamental mechanism of the adaptive immune system, where CD8+ T cells recognize specific intracellular antigens presented on the cell surface [1: Janeway's Immunobiology]. HLA-A*02:01 is a highly prevalent MHC Class I allele that presents short peptide fragments derived from endogenous proteins to the TCR [2: Marsh et al., The HLA FactsBook]. This interaction is critical for the identification and elimination of virally infected or malignant cells [3: Rossjohn et al., Annu Rev Immunol, 2015]. In oncology, this complex is targeted by engineered TCR-T cell therapies and bispecific molecules like ImmTACs, which bypass natural immune evasion by providing high-affinity recognition of tumor-specific peptides [4: Walseng et al., Immunotherapy, 2017]. Therapeutic success depends on the precise specificity of the TCR for the peptide-HLA complex to avoid off-target reactivity against similar peptides in healthy tissues [5: Linette et al., Blood, 2013]. Drugs targeting these complexes, such as Tebentafusp, redirect T-cell activity to destroy cells expressing specific antigens like gp100 [6: Nathan et al., NEJM, 2021]. Afamitresgene autoleucel is another example, targeting MAGE-A4 peptides in the context of HLA-A*02:01 to treat synovial sarcoma [7: D'Angelo et al., Lancet, 2024]. Safety concerns primarily involve cytokine release syndrome and potential cross-reactivity with non-target tissues [8: Hunter et al., J Immunother Cancer, 2021].

Other names

TCR-HLA-A*02:01 interactionpMHC-A2 complexT-cell receptor-antigen-MHC complexHLA-A*02:01-peptide-TCR

Engineered TCRs or bispecific TCR-anti-CD3 molecules bind specifically to the peptide-HLA-A*02:01 complex on target cells, leading to T-cell activation and directed lysis of the target cell.