H-2Ld class I molecule protects an HIV N-extended epitope from in vitro trimming by endoplasmic reticulum aminopeptidase associated with antigen processing.

In the classical MHC class I Ag presentation pathway, antigenic peptides derived from viral proteins by multiple proteolytic cleavages are transported to the endoplasmic reticulum lumen and are then exposed to ami-nopeptidase activity. In the current study, a long MHC class I natural ligand recognized by cytotoxic T lymphocytes was used to study the kinetics of degradation by aminopeptidase. The in vitro data indicate that this N-extended peptide is efficiently trimmed to a 9-mer, unless its binding to the MHC molecules protects the full-length peptide.We thank Dr. A. K. Stout of the NIH Tetramer Facility for providing the peptide/MHC complex reagent. This work was suppor ted by grants provi ded by Programa Ramón y Cajal, and Fundación FIPSE to D. L.; by grants provided by Comunidad de Madrid and Ministerio de Educación y Ciencia to M. D. V.; and by a joint grant provided by Instituto de Salud Carlos III to D. L., and M. D. V.S