An immunoreceptor tyrosine-based activation motif (ITAM) is a conserved sequence of four amino acids that is repeated twice in the cytoplasmic tails of non-catalytic tyrosine-phosphorylated receptors, cell-surface proteins found mainly on immune cells. [1]

Oct 23, 2017 · Here we show that the conformation and signaling of CD28 are regulated by two counteractive charged factors, acidic phospholipids and Ca 2+ ions. NMR spectroscopy analyses showed that acidic...

CD28 (Cluster of Differentiation 28) is a protein expressed on T cells that provides essential co-stimulatory signals required for T cell activation and survival. When T cells are stimulated through CD28 in conjunction with the T-cell receptor (TCR), it enhances the production of various interleukins, particularly IL-6.

We hypothesized that the redundancy of CD28 and CD3ζ signaling in a chimeric antigen receptor (CAR) design incorporating all three CD3ζ immunoreceptor tyrosine-based activation motifs (ITAMs) 11, 13 may foster counterproductive T cell differentiation and exhaustion 9, 10.

CD28, on the other hand, doesn't contain any ITAM. Instead, its cytoplasmic domain contains a YMNM motif that gets phosphorylated upon CD28 binding to its ligand CD80/CD86, which can bind to the p85 subunit of PI3K and Grb2/Gads. Additionally, proline-rich regions of CD28 can interact with Itk, Tec, Lck, Grb2/Vav, and FLNA (36, 37). Therefore ...

Nov 2, 2022 · Although co-receptor domains such as CD28 and 4-1BB do not have ITAMs, their presence mimics the co-stimulation that accompanies TCR engagement with an activated antigen-presenting cell (APC),...

Aug 1, 2020 · Multiple parameters such as CD28 co-stimulation, elevated levels of CAR expression, and aggregation-prone scFv sequences have been implicated in tonic signaling, a phenomenon that can result in early CAR-T–cell exhaustion and reduced tumor eradication.

CD28 includes at least three intracellular subdomains (YMNM, PRRP, and PYAP) that regulate costimulation post-T-cell receptor (TCR) stimulation, but it is unknown how each modulates CAR T-cell function. These three subdomains have important signaling capabilities.

CD28 domain and the kinase FYN mediate this LCK-independent signaling. LCK-disrupted CAR-T shows increased in vivo anti-tumor efficacy—attributed to the improved memory/persistence and reduced exhaustion—and the potential for allogeneic use.

May 20, 2020 · CD28-based CARs seem to elicit stronger T cell activation as compared with 4-1BB–expressing CARs, tending toward an effector-like phenotype, with high interleukin-2 (IL-2) secretion and cytolytic capacity; they are sensitive to low antigen levels and highly proliferative and glycolytic (2, 10, 11).