Cd3e, also known as CD3-epsilon, is a key component of the CD3 complex. This complex pairs with either TCR-α/TCR-β (TCRαβ) or TCR-γ/TCR-δ (TCRγδ) to form the complete αβ or γδ T cell receptor (TCR), playing a crucial role in T cell development and activation [2]. The TCR-CD3 complex is essential for the recognition of antigens presented by major histocompatibility complex (MHC) molecules, initiating downstream signaling pathways that regulate T cell functions, which are vital for the adaptive immune response [2]. Gene-edited animal models, such as Cd3e-related KO or humanized mouse models, are valuable for studying its functions in vivo.

CD3E humanized mice, established by replacing specific exons of the mouse Cd3e gene with human counterparts, expressed only human CD3E, and lymphocyte proportions in the thymus and spleen were not significantly different from wild-type mice. These mice were used to evaluate the efficacy and safety of CD3E antibody drugs. CD3E monoclonal antibody promoted tumor growth, potentially due to activation-induced cell death, while the bispecific antibody blinatumomab inhibited tumor growth, providing an in-vivo model for immunotherapy research [1]. In another study, CD3e-immunotoxin treatment preferentially depleted CD3ehi T cells, enriched tissue-resident Foxp3+ Tregs, and reshaped organ-specific T-cell composition. The differential surface expression of CD3e among T-cell subsets was a main driver of Treg enrichment [3].

In conclusion, Cd3e is essential for T cell-mediated immune responses. Model-based research, especially using CD3E humanized or immunotoxin-treated mouse models, has revealed its role in tumor immunotherapy and T-cell regulation. These findings contribute to understanding disease mechanisms and developing more effective treatments in cancer immunotherapy [1,3].

References:

1. Zhang, Rufeng, Zhang, Jing, Zhou, Xiaofei, Zhao, Ang, Yu, Changyuan. 2022. The establishment and application of CD3E humanized mice in immunotherapy. In Experimental animals, 71, 442-450. doi:10.1538/expanim.22-0012. https://pubmed.ncbi.nlm.nih.gov/35570001/

2. Morath, Anna, Schamel, Wolfgang W. 2020. αβ and γδ T cell receptors: Similar but different. In Journal of leukocyte biology, 107, 1045-1055. doi:10.1002/JLB.2MR1219-233R. https://pubmed.ncbi.nlm.nih.gov/31994778/

3. Kim, Shihyoung, Shukla, Rajni Kant, Yu, Hannah, Liyanage, Namal P M, Kim, Sanggu. 2022. CD3e-immunotoxin spares CD62Llo Tregs and reshapes organ-specific T-cell composition by preferentially depleting CD3ehi T cells. In Frontiers in immunology, 13, 1011190. doi:10.3389/fimmu.2022.1011190. https://pubmed.ncbi.nlm.nih.gov/36389741/