REQUIREMENT FOR SURFACE AMINOPEPTIDASE ACTIVITIES DURING DEVELOPMENT OF CD8(+) FETAL THYMOCYTES

The role of surface aminopeptidases (APs), enzymes that cleave amino-t erminal residues from polypeptide chains, in the development of fetal thymocytes was studied using a murine fetal thymic organ culture (FTOC ) model. FTOC AP activity was demonstrable for various amino acid-p-ni troanilide substrates, and specific inhibitors of AP (amastatin and be statin) inhibited enzymatic activity. AP activity decreased from Day 4 to Day 7 in FTOC. Inhibition of AP activity during thymic development by FTOC in the presence of bestatin caused a significant selective de crease in the percentage of CD8(+) cells (both CD4(+)CD8(+) and CD4(-) CD8(+)). Bestatin did not downregulate expression of CDS by a mature C D8(+) T cell clone. These data suggest that APs are involved in the de velopment of thymocytes expressing CD8. (C) 1997 Academic Press.