inhibitor screening kit  (BPS Bioscience)

Journal: International Journal of Molecular Sciences

Article Title: Subduing the Inflammatory Cytokine Storm

doi: 10.3390/ijms252011194

Figure Lengend Snippet: To evoke a cytokine storm, superantigen toxins must bind onto CD28 and B7 costimulatory receptor homodimer interfaces. ( A ) B7/CD28 receptor engagement is a primary immune checkpoint, essential for effective T cell activation. B7 expressed on the antigen-presenting cell (APC) engages CD28 on the T cell (arrow colors denote receptor engagement). This relatively weak interaction elicits a moderate immune signal in the T cell to induce inflammatory cytokines (orange arrows). ( B ) Bacterial superantigens induce a lethal cytokine storm by directly engaging, through their structurally conserved β-strand–hinge–α-helix domain (purple), both CD28 and B7 co-receptors at their receptor homodimer interfaces (yellow and green trapezoids) (purple arrow). Binding of a superantigen to these costimulatory receptors evokes a strong B7/CD28 interaction, thereby eliciting a powerful immune signal into the T cell that results in the induction of an inflammatory cytokine storm (red arrows) [ , , , ].

Article Snippet: To attenuate the cytokine storm underlying infection pathology, yet preserve host defenses, we uniquely targeted the engagement of CD28 with its B7 co-ligands by means of short peptide mimetics of the human CD28 and B7 receptor homodimer interfaces.

Techniques: Activation Assay, Binding Assay

Journal: International Journal of Molecular Sciences

Article Title: Subduing the Inflammatory Cytokine Storm

doi: 10.3390/ijms252011194

Figure Lengend Snippet: Mimetic peptide p 2TA , p 5TA , and p 4TA domains at the homodimer interface of costimulatory receptor CD28. In the CD28 extracellular domain sequence, peptide sequences are highlighted in yellow, with dimer interface contact residues in red. In the cartoon model of the extracellular domain of CD28 (green; 1yjd.pdb), a single beta-barrel, p 2TA is shown in sticks in dark blue with 2 dimer interface contacts in orange , p 5TA in red with 4 dimer interface contacts in yellow, and p 4TA in cyan with 3 dimer interface contacts in orange .

Article Snippet: To attenuate the cytokine storm underlying infection pathology, yet preserve host defenses, we uniquely targeted the engagement of CD28 with its B7 co-ligands by means of short peptide mimetics of the human CD28 and B7 receptor homodimer interfaces.

Techniques: Sequencing

Journal: International Journal of Molecular Sciences

Article Title: Subduing the Inflammatory Cytokine Storm

doi: 10.3390/ijms252011194

Figure Lengend Snippet: Dosed at an amount far sub-molar to the toxin, CD28 and B7-1 dimer interface mimetic peptides protect mice from lethal superantigen challenge. Peptides were injected i.p. 30 min before challenge. ( A ) Mice ( n = 5 per group) were injected with 7.5 µg SEB alone or together with 0.045 µg p 5TA (grey symbols) or 0.09 µg p 5TA (black symbols). ( B ) Mice ( n = 5 per group) were injected with 7.5 µg SEB alone or together with 0.052 µg p B1-78 (black symbols). The molar ratio SEB/peptide is shown in the color purple (reproduced after ).

Article Snippet: To attenuate the cytokine storm underlying infection pathology, yet preserve host defenses, we uniquely targeted the engagement of CD28 with its B7 co-ligands by means of short peptide mimetics of the human CD28 and B7 receptor homodimer interfaces.

Techniques: Injection

Journal: International Journal of Molecular Sciences

Article Title: Subduing the Inflammatory Cytokine Storm

doi: 10.3390/ijms252011194

Figure Lengend Snippet: Inflammatory cytokine storm: the killer. ( Top ) Through the B7/CD28 costimulatory axis, pathogens hyperactivate Th1 cells to evoke a cytokine storm (strong red arrow). ( Bottom ) Host-oriented therapeutic B7 and CD28 homodimer interface mimetic peptides attenuate B7/CD28 receptor engagement (thin green arrow) and thereby downregulate the human inflammatory Th1 cytokine response to control and prevent a cytokine storm, a strategy unlikely to be overcome by pathogen mutation. Importantly, the mimetic peptides leave a basal cytokine response intact.

Article Snippet: To attenuate the cytokine storm underlying infection pathology, yet preserve host defenses, we uniquely targeted the engagement of CD28 with its B7 co-ligands by means of short peptide mimetics of the human CD28 and B7 receptor homodimer interfaces.

Techniques: Control, Mutagenesis