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T-cell receptor specific for H-2Kb–SIINFEKL (OT-I TCR) (OT-I TCR)

Target
OT-I TCR
Molecular classification
T-cell receptor, Antigen receptor, Heterodimeric glycoprotein, Receptor
01

Overview

The T-cell receptor specific for H-2Kb–SIINFEKL, commonly known as the OT-I TCR, is a well-characterized antigen receptor used extensively in immunological research. It specifically recognizes an eight-amino acid peptide (SIINFEKL) derived from chicken ovalbumin when presented by the murine MHC class I molecule H-2Kb (Hogquist et al., 1994, Cell). This TCR is typically composed of Vα2 and Vβ5 chains and is the primary receptor expressed by CD8+ T cells in OT-I transgenic mice (The Jackson Laboratory, Stock No: 003831). In research settings, it serves as a gold-standard model for studying T-cell development, activation, and effector functions, particularly in the context of cancer immunotherapy and infectious disease (Porgador et al., 1997, Immunity). While not a direct target for small molecule drugs, it is a foundational component in the development of TCR-engineered T-cell (TCR-T) therapies and bispecific molecules designed to redirect immune responses against specific antigens (Restifo et al., 2012, Nature Reviews Immunology). The interaction between this TCR and its cognate peptide-MHC complex is often used to benchmark the affinity and sensitivity of synthetic immune receptors (Zehn et al., 2009, Nature). It also plays a critical role in understanding the mechanisms of peripheral tolerance and T-cell exhaustion in chronic disease states (Wherry et al., 2007, Nature Immunology).

Other names
OT-I T-cell receptorOVA-specific T-cell receptorH-2Kb/SIINFEKL-specific TCROT-1 TCRVα2/Vβ5 T-cell receptor
02

Mechanism of action

The TCR complex recognizes the SIINFEKL peptide presented by the H-2Kb MHC class I molecule, triggering a signaling cascade through the CD3 complex that leads to T-cell proliferation, cytokine production, and targeted lysis of antigen-presenting cells (Hogquist et al., 1994, Cell).

03

Biological functions

Antigen recognitionT-cell activationImmune responseCytotoxicitySignal transduction
04

Disease associations

CancerInfectionAutoimmunity
05

Safety considerations

On-target off-tumor toxicityCytokine release syndromeCross-reactivity with self-peptidesGraft-versus-host disease
06

Interacting drugs

TCR-T cell therapies

4 more in the full profile.

07

Biomarkers

H-2Kb/SIINFEKL tetramer bindingCD8 expressionInterferon-gamma productionCD69 expressionVα2/Vβ5 TCR chain expression

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