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Effects of CD28/B7 pathway on PD-1/PD-L1 immunotherapy

Time: 2017-04-10 10:43:03

Effects of CD28/B7 pathway on PD-1/PD-L1 immunotherapy
2017-04-10   www.fn-test.com


T cell activation requires two signals: TCR signal and costimulatory signal (such as CD28), and T cell surface is also co inhibitory factor (such as PD-1), as a checkpoint to maintain immune homeostasis.

At present, most scientists believed that PD-1 blockade can reverse the failure of T cells (loss of function) by inhibiting TCR signal transduction, but not in the activation and effect or phase of T cell response. PD-1 blockade can also target the T cells which are not damaged, and they also play a role in the early stage of T cell
response and immune surveillance.

The researchers found that CD28 and PD-1 in the interaction of PD-1 and PD-L1 in the 30s in the vicinity of the TCR will be a short aggregation of the cluster, is conducive to the activation of PD-1 dephosphorylation of CD28. The combination of PD-1 and PD-L1 can lead to two kinds of tyrosine PD-1 cytoplasmic domain in (Y224 and Y248) in phosphate kinase Lck action, and then raised cytosolic tyrosine phosphatase SHP2 to PD-1 and CD28 dephosphorylation, and termination of CD28 signaling and regulating immune suppression function.

In the intact cell system, CD28 is preferentially phosphorylated in PD-1 activation compared to TCR, which indicates that PD-1 can inhibit the function of T cells by inactivating the CD28 signal.

At the same time, Professor Kamphorst also demonstrated that the CD28/B7 costimulatory pathway is required for effective PD-1 therapy and PD-1+ CD8 T cell proliferation in chronic viral infection and cancer mouse models.

After the activation of PD-1 can directly target the cytoplasmic region of CD28, and has a higher ratio of T cell receptor downstream molecular affinity, further emphasizes the interaction between CD28 and PD-1 pathways, PD-1 for molecular
targeted immunotherapy interactions provides new insights.

Related products for PD-1/PD-L1 immunotherapy

  • ELISA KITS

EH0653 Human CD28(T-cell-specific surface glycoprotein CD28) ELISA Kit

ER0814 Rat CD28 (Cluster of Differentiation 28) ELISA Kit

EH3528 Human PDCD1LG1 (Programmed Cell Death Protein 1 Ligand 1) ELISA Kit

EM0399
Mouse CD274(Programmed cell death 1 ligand 1) ELISA Kit

ER1238 Rat PDCD1LG1 (Programmed Cell Death Protein 1 Ligand 1) ELISA Kit

  • Antibodies

FNab06281  Anti- PD-L1/CD274 Antibody

Reference

T cell costimulatory receptor CD28 is a primary target for PD-1–mediated inhibition

1.   Science  31 Mar 2017:

Vol. 355, Issue 6332, pp. 1428-1433
DOI: 10.1126/science.aaf1292

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