The carboxypeptidase ACE shapes the MHC class i peptide repertoire

Xiao Z. Shen, Sandrine Billet, Chentao Lin, Derick Okwan-Duodu, Xu Chen, Aron E. Lukacher, Kenneth E. Bernstein

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

The surface presentation of peptides by major histocompatibility complex (MHC) class I molecules is critical to CD8 + T cell-mediated adaptive immune responses. Aminopeptidases have been linked to the editing of peptides for MHC class I loading, but carboxy-terminal editing is thought to be due to proteasome cleavage. By analysis of wild-type mice and mice genetically deficient in or overexpressing the dipeptidase angiotensin-converting enzyme (ACE), we have now identified ACE as having a physiological role in the processing of peptides for MHC class I. ACE edited the carboxyl terminus of proteasome-produced MHC class I peptides. The lack of ACE exposed new antigens but also abrogated some self antigens. ACE had substantial effects on the surface expression of MHC class I in a haplotype-dependent manner. We propose a revised model of peptide processing for MHC class I by introducing carboxypeptidase activity into the process.

Original languageEnglish (US)
Pages (from-to)1078-1085
Number of pages8
JournalNature Immunology
Volume12
Issue number11
DOIs
StatePublished - Nov 2011

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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