T lymphocytes are an important part of the body's immune system. The activation of T cells can resist the invasion of tumor cells and pathogenic bodies, but also lead to autoimmune diseases due to overactivation.
T cell activation is a complex process, including receiving signal stimulation, signal transduction, intracellular enzyme activation, gene transcription expression and cell amplification.
T cell activation requires dual signal stimulation.
First signal: antigen peptide -MHC molecular complex on antigen presenting cells binds to TCR specifically.
Second signal: interaction between T cells and costimulatory molecules present on the surface of antigen presenting cells produces costimulatory signals, of which CD28 and B7(CD80/CD86) are relatively important.
The integration of the two signals was the most effective way to induce T cell activation, while the lack of costimulation signals resulted in decreased T cell response, and in some cases can induce tolerance or T cell anergy. Blocking the co-stimulus signal of T cell activation can negatively regulate T cell activity and induce T cell immune tolerance.
Intracellular signaling is accomplished by the following kinases and phosphatases. The molecules involved in TCR signal transduction mainly include upstream kinases (Lck, Fyn, ZAP-70, Itk), scaffold proteins (LAT, Gads, SLP-76, Grb2), phospholipases, phosphatases, etc. Activation of TCR signals not only induces T cell proliferation and cytokine production, but also promotes T cell differentiation and T cell function.
The T cell receptor is located on the surface of T cells, which specifically recognizes antigenic peptides presented by MHC on the surface of antigen-presenting cells, and activates signal pathways such as ERK, JNK, and NF-κB in T cells. Through several different signaling pathways, many transcription factors associated with cell division and differentiation are activated to regulate cell functions such as T cell proliferation, differentiation, death, and cytokine release. Typical intracellular signals activated by TCR also include: MAPK (Mitogen-activated protein kinase), PKC (Protein Kinase C), calcium signal pathways.