Endoplasmic reticulum aminopeptidase associated with antigen processing defines the composition and structure of MHC class I peptide repertoire in normal and virus-infected cells

Nicolas Blanchard, Takayuki Kanaseki, Hernando Escobar, Frédéric Delebecque, Niranjana A. Nagarajan, Eduardo Reyes-Vargas, David K. Crockett, David H. Raulet, Julio C. Delgado, Nilabh Shastri

Research output: Contribution to journalArticlepeer-review

Abstract

The MHC class I (MHC-I) molecules ferry a cargo of peptides to the cell surface as potential ligands for CD8+ cytotoxic T cells. For nearly 20 years, the cargo has been described as a collection of short 8-9 mer peptides, whose length and sequences were believed to be primarily determined by the peptide-binding groove of MHC-I molecules. Yet the mechanisms for producing peptides of such optimal length and composition have remained unclear. In this study, using mass spectrometry, we determined the amino acid sequences of a large number of naturally processed peptides in mice lacking the endoplasmic reticulum aminopeptidase associated with Ag processing (ERAAP). We find that ERAAP-deficiency changed the oeuvre and caused a marked increase in the length of peptides normally presented by MHC-I. Furthermore, we observed similar changes in the length of viral peptides recognized by CD8+ T cells in mouse CMV-infected ERAAP-deficient mice. In these mice, a distinct CD8 + T cell population was elicited with specificity for an N-terminally extended epitope. Thus, the characteristic length, as well as the composition of MHC-I peptide cargo, is determined not only by the MHC-I peptide-binding groove but also by ERAAP proteolysis in the endoplasmic reticulum.

Original languageEnglish (US)
Pages (from-to)3033-3042
Number of pages10
JournalJournal of Immunology
Volume184
Issue number6
DOIs
StatePublished - Mar 15 2010

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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