P140

P140 is a peptide from the small nuclear ribonucleoprotein U1-70K, phosphorylated at the Ser140 position. P140 binds to the HSPA8/HSC70 chaperone protein, a constitutively expressed, cognate protein of the HSP70 family, which is involved in many cellular processes and has a key regulatory role in autophagy. Both in vitro and in vivo, P140 interferes with hyperactivated chaperone-mediated autophagy, modifying overexpression of major histocompatibility complex class II molecules and antigen presentation to autoreactive T cells. In a lupus prone murine model, P140 displays tolerogenic and immunomodulatory effects, depleting hyperactivated autoreactive T and B cells and restoring normal immune homeostasis. P140 decreases proteinuria and anti-DNA antibody production, and significantly prolongs survival.