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Exploring the secrets of T cells: How to recognize foreign antigens and ignore self-antigens?
T cells are lymphocytes that play a key role in the immune system. The T cell receptor (TCR) is a protein complex located on the surface of T cells that is responsible for recognizing antigen fragments. This ability involves not only an effective response to foreign antigens, but more importantly, the ability of T cells to remain calm among multiple self-antigens, thereby preventing mistaken attacks on the body's own tissues. How this process is achieved remains an important topic for scientific research.
An effective T cell response enables our immune system to quickly fight abnormal cells such as pathogens and tumors.
Structure and function of T cell receptor (TCR)
TCR is mainly composed of two chains, α and β, and this heterodimeric structure accounts for 95% of the vast majority of human T cells. When TCRs bind to antigen-major histocompatibility complex (pMHC), they initiate a signal transduction process that leads to T cell activation. The binding affinity of TCR is relatively low, but its diversity comes from a large amount of genetic recombination and the generation of new antigen specificity.
Generation of TCR Diversity
The diversity of TCR is similar to the generation of antibodies (BCR), which is mainly achieved through genetic recombination. During early lymphocyte development, the α and β chains of TCRs undergo random V(D)J recombination to generate TCRs with unique antigen specificity. This recombination process endows T cells with enormous antigen recognition capabilities; however, unlike antibodies, TCR genes do not undergo somatic hypermutation.
This unique antigen recognition ability ensures that T cells do not accidentally damage their own normal cells while fighting pathogens.
Mechanisms of antigen recognition
One of the functions of T cells is the ability to distinguish between healthy cells and abnormal cells. In most cases, antigen-presenting cells do not distinguish between self-antigens and foreign antigens, but T cells have a certain affinity for self-antigens when they undergo positive selection in the thymus. Therefore, TCR activation does not trigger an immune response due to binding to self-antigens.
Signal transduction process
When TCR recognizes pMHC, a series of signal transduction processes are initiated, leading to the activation of T cells. An important link in this process is the phosphorylation of ITAM (immunoreceptor tyrosine-based activation motif), which in turn recruits downstream signaling molecules such as Zap70. This enables the T cells to respond quickly and transform into effector T cells or memory T cells.
Activated T cells can release cytokines, proliferate, and exhibit cytotoxicity to fight abnormal pathogens in the body.
Clinical potential and future research directions
Current research has extended to the use of TCR in cancer immunotherapy, especially CAR-T therapy, which has shown significant effects in the treatment of certain cancers. In the future, a deeper understanding of the mechanism of TCR will not only improve the effectiveness of cancer treatment, but also enhance the accuracy of vaccine design. How to enable T cells to more effectively identify and attack tumor cells will be an important direction for future research.
In this context of the increasingly recognized importance of the role of T cells, we cannot help but wonder, in the face of infinite antigen diversity, how does the T cell recognition mechanism work in a complex immune environment?
