Description
OT-1 mice: Biological Roles and Therapeutic Strategies
- Gene Information: The OT-I model contains transgenic inserts encoding mouse rearranged TCR alpha (Tcra-V2) and beta (Tcrb-V5) chains driven by endogenous and MHC class I promoter elements.
- Protein Expression: Transgenic TCR expression is skewed overwhelmingly toward CD8⁺ T cells, generating a high-frequency, clonal population of CD8⁺ effector T cells with transgenic Vα2/Vβ5 TCR complexes.
- Signaling Pathway: Cognate binding of the transgenic TCR to the chicken ovalbumin-derived peptide OVA257-264 (SIINFEKL) presented on MHC class I (H-2Kb) initiates LCK/ZAP-70 downstream cascade signaling, driving robust CD8⁺ T-cell activation, proliferation, and cytotoxic granule release.
- Therapeutic Inhibition: Therapeutic and functional studies utilize the model via adoptive cell transfer, co-culture assays, or OVA-expressing tumor/pathogen challenge to evaluate antigen-specific T-cell responses, TCR-based therapeutics, immune checkpoint inhibitors, and CAR-T/TCR-T cytotoxic efficacy.
Targeting strategy
OT-1 mice
The BAC containing the whole sequence of mouse Trav2 gene was inserted into Hipp11 locus and the BAC containing the whole sequence of mouse Trbv5 gene was inserted into Rosa26 locus in OT-1 mice.
The Increasing CD8+ T/CD4+ T Cells Ratio
The CD8+ T/CD4+ T ratio between wild-type C57BL/6JNifdc mice and homozygous OT-1 mice. Splenocytes, blood and lymph nodes were collected from wild-type C57BL/6JNifdc mice and homozygous OT-1 mice (male, 8-week-old).
TCR Vα2 and Vβ5 Protein Expression Analysis
Strain specific mouse TCR Vα2 and TCR Vβ5 expression analysis in wild-type C57BL/6JNifdc mice and homozygous OT-1 mice by flow cytometry. Splenocytes were collected from wild-type C57BL/6JNifdc mice and homozygous OT-1 mice, and analyzed by flow cytometry with species-specific anti-mTCR Vα2 antibody (BioLegend, 127807) and anti-mTCR Vβ5.1, 5.2 antibody (BioLegend, 139505).
* When publishing results obtained using this animal model, please acknowledge the source as follows: The animal model [OT-1 mice] (Cat# 113877) was purchased from Biocytogen.
