CD3 protein is one of the key molecules in the immune system, involved in activating cytotoxic T cells (CD8+ naive T cells) and T helper cells (CD4+ naive T cells), responsible for monitoring and resisting infections and abnormal cells in the body.

Definition and structure of CD3:

CD3 is composed of four different chains: CD3δ, CD3ε, CD3γ, and CD3ζ. CD3δ/CD3ε, CD3γ/CD3ε, and CD3ζ can form a TCR-CD3 complex through the α/β chains of the TCR, generating activation signals in T lymphocytes.

Activation of T lymphocytes:

When T cells encounter antigens presented by the major histocompatibility complex (MHC), changes in the complex's conformation lead to phosphorylation of the CD3 peptide chain, initiating a series of signal transduction pathways. These signal transduction processes ultimately lead to T cell activation, producing a series of biological effects such as cell proliferation, differentiation, and cytokine production. The CD3 protein plays a bridging role in this signal transduction process, ensuring that T cells mount an appropriate immune response to specific antigens.

(Data source: www.researchgate.net/publication/286296142)

Regulation of immune response:

The CD3 protein not only plays a role in T cell activation but also regulates the intensity and duration of the immune response. Once the antigen is cleared, the CD3 protein helps maintain the balance of the immune system through a negative feedback mechanism, preventing overactivation that can lead to autoimmune diseases and other problems.

(Data source: Acuto O, et al. Nat Rev Immunol. 2008)

Clinical application:

The CD3 protein has important clinical applications in medicine. For example, CAR-T cell therapy, a form of immunotherapy, leverages knowledge of CD3ζsignaling to engineer artificial T cells that can more effectively recognize and attack tumor cells. This therapy has achieved remarkable results in the treatment of certain leukemias and lymphomas.

(Data source: June CH, et al. Science. 2018)

Alternatively, multispecific antibodies targeting CD3 can be designed to simultaneously bind to CD3 molecules on the surface of CD3 T cells and antigens on the surface of target cells. This multispecificity allows CD3 multispecific antibodies to directly connect T cells and target tumor cells to exert cell-killing effects while promoting T cell-mediated cytotoxicity.

(Data source: Garfall AL, et al. Nature. 2019)

In addition to its key role in signal transduction, CD3 also plays a crucial role in T cell development and differentiation. In the thymus, CD3 expression is a key marker for T cell development and maturation. Overall, as a key molecule in T cell activation and regulation, CD3 protein holds significant significance in immunology and medical research. In-depth research on it contributes to our understanding of the mechanisms of immune response and provides new insights and approaches for disease treatment.