In the absence of aminopeptidase ERAAP, MHC class I molecules present many unstable and highly immunogenic peptides

Gianna Elena Hammer, Federico Gonzalez, Edward James, Hector Nolla, Nilabh Shastri

Research output: Contribution to journalArticle

Abstract

Immunosurveillance by cytotoxic T cells requires that cells generate a diverse spectrum of peptides for presentation by major histocompatibility complex (MHC) class I molecules. Those peptides are generated by proteolysis, which begins in the cytoplasm and continues in the endoplasmic reticulum by the unique aminopeptidase ERAAP. The overall extent to which trimming by ERAAP modifies the peptide pool and the immunological consequences of ERAAP deficiency are unknown. Here we show that the peptide-MHC repertoire of ERAAP-deficient mice was missing many peptides. Furthermore, ERAAP-deficient cells presented many unstable and structurally unique peptide-MHC complexes, which elicited potent CD8+ T cell and B cell responses. Thus, ERAAP is a 'quintessential editor' of the peptide-MHC repertoire and, paradoxically, its absence enhances immunogenicity.

Original languageEnglish (US)
Pages (from-to)101-108
Number of pages8
JournalNature Immunology
Volume8
Issue number1
DOIs
StatePublished - Jan 1 2007
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'In the absence of aminopeptidase ERAAP, MHC class I molecules present many unstable and highly immunogenic peptides'. Together they form a unique fingerprint.

  • Cite this