title: Extracellular processing of peptide antigens that bind class I major histocompatibility molecules.
abstract: One problem associated with the use of synthetic peptides as antigens in vivo is their susceptibility to inactivation by proteolytic degradation. A situation is described in which a serum protease, angiotensin-converting enzyme (ACE), is actually responsible for the class I binding activity of a commonly used influenza antigen, nucleoprotein (NP)(147-158R-). This peptide has been reported to be a highly efficient class I antigen. Evidence is presented that demonstrates that the peptide is inactive until cleaved by ACE, which is a normal constituent of serum. The enzyme removes a COOH-terminal dipeptide resulting in the sequence NP(147-155), which is identical to the naturally processed peptide. Such extracellular processing of peptides and proteins may occur for a variety of antigens both in vitro and in vivo, and could have important implications for the design of proteolytically resistant vaccines.
authors.affiliation: Department of Immunology, Scripps Research Institute, La Jolla, California 92037.
authors.forename: L A
authors.initials: LA
authors.lastname: Sherman
authors.forename: T A
authors.initials: TA
authors.lastname: Burke
authors.forename: J A
authors.initials: JA
authors.lastname: Biggs
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D002852:Chromatography, Ion Exchange; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009698:Nucleoproteins / Q000378:metabolism; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D001613:beta 2-Microglobulin / Q000378:metabolism
chemical_list: D000941:Antigens; D015395:Histocompatibility Antigens Class I; D009698:Nucleoproteins; D010455:Peptides; D001613:beta 2-Microglobulin; D007703:Peptidyl-Dipeptidase A