Title

Distinct proteolytic processes generate the C and N termini of MHC class I-binding peptides

UMMS Affiliation

Department of Pathology

Date

11-26-1999

Document Type

Article

Subjects

Aminopeptidases; *Antigen Presentation; Cysteine Endopeptidases; Cysteine Proteinase Inhibitors; Histocompatibility Antigens Class I; *Major Histocompatibility Complex; Multienzyme Complexes; Nucleocapsid Proteins; Nucleoproteins; Oligopeptides; Peptide Fragments; Proteasome Endopeptidase Complex; Protein Binding; Viral Core Proteins; Viral Proteins

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

Most of the MHC class I peptides presented to the immune system are generated during the course of protein breakdown by the proteasome. However, the precise role of the proteasome, e.g., whether this particle or some other protease generates the carboxyl (C) and amino (N) termini of the presented 8- to 10-residue peptides, is not clear. Here, we show that presentation on Db of ASNENMETM, a peptide from influenza nucleoprotein, and on Kb of FAPGNYPAL, a peptide from Sendai virus nucleoprotein, was blocked by the proteasome inhibitor, lactacystin. Using plasmid minigene constructs encoding oligopeptides of various lengths, we found that presentation of ASNENMETM from C-terminally extended peptides that contain this antigenic peptide plus three or five additional amino acids and presentation of FAPGNYPAL from a peptide containing FAPGNYPAL plus one additional C-terminal residue required the proteasome. In contrast, the proteasome inhibitor did not reduce presentation of cytosolically expressed ASNENMETM or FAPGNYPAL or N-terminally extended versions of these peptides, suggesting involvement of aminopeptidase(s) in trimming these N-extended variants. Accordingly, when the N termini of these 3N-extended peptides were blocked by acetylation, they were resistant to hydrolysis by cellular aminopeptidases and pure leucine aminopeptidase. Moreover, if introduced into the cytosol, Ag presentation of these peptides occurred to a much lesser extent than from their nonacetylated counterparts. Thus, the proteasome is essential for the generation of ASNENMETM and FAPGNYPAL peptides from the full-length nucleoproteins. Although it generates the C termini of these presented peptides, distinct aminopeptidase(s) can trim the N termini of these presented peptides to their proper size.

Rights and Permissions

Citation: J Immunol. 1999 Dec 1;163(11):5851-9.

Related Resources

Link to Article in PubMed

PubMed ID

10570269