Endoplasmic reticulum aminopeptidase associated with antigen processing regulates quality of processed peptides presented by MHC class I molecules

Takayuki Kanaseki, Nilabh Shastri

Research output: Contribution to journalArticle

Abstract

Effective immune surveillance by CD8 T cells depends on the presentation of diverse peptides by MHC class I (pMHC I) molecules on the cell surface. The pMHC I repertoire is shaped in the endoplasmic reticulum (ER) by the ER aminopeptidase associated with Ag processing (ERAAP). The ERAAP activity is required for producing peptides of appropriate length for generating optimal pMHC I. Paradoxically, ERAAP also inhibits generation of certain peptides such as the SVL9 (SSVVGVWYL) peptide encoded by the H13a histocompatibility gene and presented by Db MHC by an unknown mechanism. In this study, we show that the presentation of the SVL9-D b complex is inhibited when other peptides compete for binding D b. Conversely, improving the binding of SVL9 peptide to Db suppresses the inhibition. Interestingly, the inhibitory effect of competitor peptides is observed only when ERAAP is expressed in the same cells. Thus, ERAAP, in concert with MHC I molecules, regulates the quality of processed peptides presented on the cell surface.

Original languageEnglish (US)
Pages (from-to)6275-6282
Number of pages8
JournalJournal of Immunology
Volume181
Issue number9
DOIs
StatePublished - Nov 1 2008

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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