A monoclonal antibody targeted to the functional peptide of αB-crystallin inhibits the chaperone and anti-apoptotic activities.

αB-Crystallin is a member of the small heat shock protein family. It is a molecular chaperone and an anti-apoptotic protein. Previous studies have shown that the peptide (73DRFSVNLDVKHFSPEELKVKV93, hereafter referred to as peptain-1) from the core domain of αB-crystallin exhibits both chaperone and anti-apoptotic properties similar to the parent protein. We developed a mouse monoclonal antibody against peptain-1 with the aim of blocking the functions of αB-crystallin. The antibody reacted with peptain-1, it did not react with the chaperone peptide of αA-crystallin. The antibody strongly reacted with human recombinant αB-crystallin but weakly with Hsp20; it did not react with αA-crystallin or Hsp27. The antibody specifically reacted with αB-crystallin in human and mouse lens proteins but not with αA-crystallin. The antibody reacted with αB-crystallin in human lens epithelial cells, human retinal endothelial cells, and with peptain-1 in peptain-1-transduced cells. Unlike the commercial antibodies against αB-crystallin, the antibody against peptain-1 inhibited the chaperone and anti-apoptotic activities of peptain-1. The antibody might find use in inhibiting αB-crystallin's chaperone and anti-apoptotic activities in diseases where αB-crystallin is a causative or contributing factor.