Immune surveillance of immune surveillance

Abstract

The peptide repertoire presented by classical MHC Ia molecules is critical for immune surveillance of intracellular pathogens and cancer. The presentation of this normal peptide repertoire is regulated by ERAAP, the ER aminopeptidase associated with antigen processing. Changes in ERAAP function cause profound changes in the presented peptides that can potentially cause autoimmunity or alter the efficacy of immunotherapy of cancer. Thus, an unusual subset of CD8+ T cells monitors normal ERAAP function. Cells with compromised ERAAP activity present the QFL ligand that contains a highly conserved FL9 peptide presented by Qa-1b, a non-classical MHC Ib molecule expressed. The QFL-specific CD8+ T cells bear highly conserved αβ TCRs and have distinct anatomical locations as well as functions. Together these features implicate QFL-specific cells in carrying out immune surveillance of the MHC Ia immune surveillance pathway.