The partial dissociation of MHC class I-bound peptides exposes their N terminus to trimming by endoplasmic reticulum aminopeptidase 1.

ABSTRACT: Endoplasmic reticulum aminopeptidase 1 (ERAP1) and ERAP2 process N-terminally extended antigenic precursors for optimal loading onto major histocompatibility complex class I (MHC I) molecules. We and others have demonstrated that ERAP1 processes peptides bound to MHC I, but the underlying mechanism is unknown. To this end, we utilized single-chain trimers (SCT) of the ovalbumin-derived epitope SIINFEKL (SL8) tethered to the H2-K^b MHC I determinant from mouse and introduced three substitutions, E63A, K66A, and W167A, at the A-pocket of the peptide-binding groove in the MHC I heavy chain, which interact with the N termini of peptides. These variants significantly decreased SL8-presenting SCT at the cell surface in the presence of ERAP1, but did not affect overall SCT expression, i

SUBMITTER: Papakyriakou A 

PROVIDER: S-EPMC5961055 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature