ERAAP Synergizes with MHC Class I Molecules to Make the Final Cut in the Antigenic Peptide Precursors in the Endoplasmic Reticulum

Takayuki Kanaseki, Nicolas Blanchard, Gianna Elena Hammer, Federico Gonzalez, Nilabh Shastri

Research output: Contribution to journalArticle

Abstract

The major histocompatibility complex class I molecules display peptides (pMHC I) on the cell surface for immune surveillance by CD8+ T cells. These peptides are generated by proteolysis of intracellular polypeptides by the proteasome in the cytoplasm and then in the endoplasmic reticulum (ER) by the ER aminopeptidase associated with antigen processing (ERAAP). To define the unknown mechanism of ERAAP function in vivo, we analyzed naturally processed peptides in cells with or without appropriate MHC I and ERAAP. In the absence of MHC I, ERAAP degraded the antigenic precursors in the ER. However, MHC I molecules could bind proteolytic intermediates and were essential for generation of the final peptide by ERAAP. Thus, ERAAP synergizes with MHC I to generate the final pMHC I repertoire.

Original languageEnglish (US)
Pages (from-to)795-806
Number of pages12
JournalImmunity
Volume25
Issue number5
DOIs
StatePublished - Nov 1 2006

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Keywords

  • MOLIMMUNO
  • PROTEINS

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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