SARS Coronavirus Fusion Peptide-Derived Sequence Suppresses Collagen-Induced Arthritis in DBA/1J Mice

Shen, Zu T.; Sigalov, Alexander B.

When intraperitoneally (i.p.) administered daily at a dose of 25 mg/kg, MG11 significantly suppressed arthritis severity compared with administration of vehicle or control peptide MG11-2G (25 mg/kg/day). As shown in Fig. 2a , the difference between the MG11 and vehicle groups started on day 28 and continued until day 38. On day 38, the mean ± SEM clinical arthritis score in MG11-treated mice with CIA was much lower than that in MG11-2G-treated mice (0.89 ± 0.30 versus 3.16 ± 0.47; P < 0.001). The effect is dose-dependent: no anti-arthritic activity was observed for free MG11 i.p. administered daily at a dose of 2.5 mg/kg (data not shown). The TCR α and β recognition subunits are shown in red and blue, respectively. The CD3ε , CD3δ , CD3γ and ζ signaling subunits are shown as purple, dark orange, light orange and green, respectively. Immunoreceptor tyrosine-based activation motifs (ITAMs) are shown as spheres and are colored accordingly by subunit. The recognition and signaling subunits are bound together by electrostatic transmembrane (TM) interactions. These TM interactions occur between basic and acidic amino acid residues. The TCRα transmembrane domain (TMD) contains two basic residues: a lysine, which interacts with two acidic residues of aspartic acid present in the TMDs of the CD3ε δ heterodimer, and an arginine, which interacts with two aspartic acid residues present in the TMDs of the ζ ζ homodimer. The TCRβ TMD contains a lysine, which interacts with one aspartic acid residue and one acidic residue of glutamic acid present in the TMDs of the CD3ε γ heterodimer. (b) TMtargeted SCHOOL peptides such as the SARS-CoV FP or the TCR CP disrupt TM electrostatic interactions between the TCRα subunit and both CD3ε δ and ζ ζ by competing with TCRα for binding to CD3ε δ and ζ ζ .