Marlene Bouvier
University of Illinois at Chicago, Franc
Title: ERAP1-ERAP2 dimers trim MHC I-bound precursor peptides; understanding peptide editing
Biography
Biography: Marlene Bouvier
Abstract
Statement of the Problem: The human endoplasmic reticulum aminopeptidase 1 (ERAP1) and ERAP2 are critically important in the final processing of MHC class I antigens in the endoplasmic reticulum. To date, the molecular context of peptide trimming by ERAPs, and how ERAPs shape antigen repertoires, remain open questions. Methodology: Using a cell-free system composed of ERAP1 and ERAP2 heterodimers (ERAP1/2), MHC class I molecules, and N-terminally extended model and natural peptides, we characterized the function of ERAP1/2. Findings: We provide evidence that ERAP1/2 trims MHC I-bound precursor peptides to the final lengths, albeit more slowly than the corresponding free precursors. We show that trimming of MHC I-bound precursors by ERAP1/2 increases the conformational stability of MHC I/peptide complexes. Conclusion & Significance: Our study provides new findings on ERAP1/2 as a key antigen processing complex. From our data, we propose a molecular mechanistic model of ERAP1/2 as an editor of class I antigens. Understanding class I antigen processing is significant given the role that class I antigens play in the normal recognition of virally infected and transformed cells by CD8+ T cells.