Nonclassical MHC class Ib-restricted cytotoxic T cells monitor antigen processing in the endoplasmic reticulum

Niranjana A. Nagarajan, Federico Gonzalez, Nilabh Shastri

Research output: Contribution to journalArticle

Abstract

The aminopeptidase ERAAP is essential for trimming peptides presented by major histocompatibility complex (MHC) class I molecules. Inhibition of ERAAP by cytomegalovirus results in evasion of the immune response by this virus, and polymorphisms in ERAAP are associated with autoimmune disorders. How normal ERAAP function is monitored is unknown. We found that inhibition of ERAAP rapidly induced presentation of the peptide FYAEATPML (FL9) by the MHC class Ib molecule Qa-1b. Antigen-experienced T cells specific for the Qa-1b-FL9 complex were frequent in naive mice. Wild-type mice immunized with ERAAP-deficient cells mounted a potent CD8+ T cell response specific for Qa-1b-FL9. MHC class Ib-restricted cytolytic effector cells specifically eliminated ERAAP-deficient cells in vitro and in vivo. Thus, nonclassical Qa-1b-peptide complexes direct cytotoxic T cells to targets with defective antigen processing in the endoplasmic reticulum.

Original languageEnglish (US)
Pages (from-to)579-586
Number of pages8
JournalNature Immunology
Volume13
Issue number6
DOIs
StatePublished - Jun 1 2012

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Nonclassical MHC class Ib-restricted cytotoxic T cells monitor antigen processing in the endoplasmic reticulum'. Together they form a unique fingerprint.

  • Cite this