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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Hammer, GE; Gonzalez, F; James, E; Nolla, H; Shastri, N

Published Date

  • January 1, 2007

Published In

Volume / Issue

  • 8 / 1

Start / End Page

  • 101 - 108

PubMed ID

  • 17128277

Pubmed Central ID

  • 17128277

International Standard Serial Number (ISSN)

  • 1529-2908

Digital Object Identifier (DOI)

  • 10.1038/ni1409

Language

  • eng

Conference Location

  • United States