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T-cell receptor specific for SARS-CoV-2 spike peptide-MHC complex (Spike-specific TCR) (Spike-specific TCR)

Target
Spike-specific TCR
Molecular classification
Receptor, T-cell receptor, Heterodimeric protein, Immune receptor
01

Overview

T-cell receptors (TCRs) specific for spike-derived peptide-MHC complexes are specialized immune receptors that recognize fragments of the SARS-CoV-2 spike protein presented by Human Leukocyte Antigen (HLA) molecules. These receptors are primarily found on CD8+ cytotoxic T cells and CD4+ helper T cells, where they play a pivotal role in identifying and orchestrating the destruction of virus-infected cells (PubMed: 32887277). The interaction between the TCR and the peptide-MHC complex is highly specific, often targeting immunodominant epitopes like the S269-277 peptide in HLA-A*02:01 individuals (Nature: 10.1038/s41586-020-2550-z). In therapeutic development, these TCRs are utilized in TCR-T cell therapy, a form of adoptive immunotherapy where a patient's T cells are genetically engineered to express these specific receptors to enhance viral clearance (PubMed: 33544858). They also serve as critical biomarkers for assessing the cellular immune response following vaccination or natural infection (NIH: PMC7518924). However, the clinical application of spike-specific TCRs faces challenges such as HLA restriction, which limits the therapy to specific genetic populations, and the potential for cross-reactivity with endogenous human proteins, which could lead to autoimmunity (PubMed: 34103407).

Other names
SARS-CoV-2 spike-reactive T-cell receptorAnti-spike TCRSpike-peptide-specific TCRSARS-CoV-2 spike-specific TCR
02

Mechanism of action

Recognition of SARS-CoV-2 spike protein-derived peptides presented by specific Human Leukocyte Antigen (HLA) molecules, triggering T-cell signaling and effector functions such as cytokine release and lysis of infected cells.

03

Biological functions

Immune responseAntigen recognitionT-cell activationCell-mediated cytotoxicityCytokine production
04

Disease associations

InfectionCOVID-19
05

Safety considerations

Cross-reactivity with self-antigens (molecular mimicry)Cytokine release syndrome (CRS)HLA restriction limiting patient eligibilityImmune evasion via viral mutation in spike epitopes
06

Interacting drugs

TCR-T cell therapy (experimental)

3 more in the full profile.

07

Biomarkers

MHC-peptide multimer bindingInterferon-gamma (IFN-g) productionTCR repertoire sequencingCD137 expressionCD154 expression

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