The carboxypeptidase ACE shapes the MHC class i peptide repertoire

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

Research output: Contribution to journalArticle

44 Citations (Scopus)

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 1 2011

Fingerprint

Carboxypeptidases
Peptidyl-Dipeptidase A
Major Histocompatibility Complex
Peptides
Proteasome Endopeptidase Complex
Aminopeptidases
Autoantigens
Adaptive Immunity
Haplotypes
T-Lymphocytes
Antigens

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Shen, X. Z., Billet, S., Lin, C., Okwan-Duodu, D., Chen, X., Lukacher, A., & Bernstein, K. E. (2011). The carboxypeptidase ACE shapes the MHC class i peptide repertoire. Nature Immunology, 12(11), 1078-1085. https://doi.org/10.1038/ni.2107
Shen, Xiao Z. ; Billet, Sandrine ; Lin, Chentao ; Okwan-Duodu, Derick ; Chen, Xu ; Lukacher, Aron ; Bernstein, Kenneth E. / The carboxypeptidase ACE shapes the MHC class i peptide repertoire. In: Nature Immunology. 2011 ; Vol. 12, No. 11. pp. 1078-1085.
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Shen, XZ, Billet, S, Lin, C, Okwan-Duodu, D, Chen, X, Lukacher, A & Bernstein, KE 2011, 'The carboxypeptidase ACE shapes the MHC class i peptide repertoire', Nature Immunology, vol. 12, no. 11, pp. 1078-1085. https://doi.org/10.1038/ni.2107

The carboxypeptidase ACE shapes the MHC class i peptide repertoire. / Shen, Xiao Z.; Billet, Sandrine; Lin, Chentao; Okwan-Duodu, Derick; Chen, Xu; Lukacher, Aron; Bernstein, Kenneth E.

In: Nature Immunology, Vol. 12, No. 11, 01.11.2011, p. 1078-1085.

Research output: Contribution to journalArticle

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Shen XZ, Billet S, Lin C, Okwan-Duodu D, Chen X, Lukacher A et al. The carboxypeptidase ACE shapes the MHC class i peptide repertoire. Nature Immunology. 2011 Nov 1;12(11):1078-1085. https://doi.org/10.1038/ni.2107