ER aminopeptidases generate a unique pool of peptides for MHC class I molecules

Nat Immunol. 2001 Jul;2(7):644-51. doi: 10.1038/89800.


We define here the specificity and significance of proteases in the endoplasmic reticulum (ER) that generate peptides for presentation by major histocompatibility complex (MHC) class I molecules. We show that aminopeptidases efficiently trimmed all residues except proline that flank the NH2-termini of antigenic precursors in the ER and caused an accumulation of X-P-Xn peptides. An aminopeptidase inhibitor blocked peptide trimming in the ER and, consequently, the generation of peptide-loaded MHC molecules. Peptide trimming in the ER is therefore a key step in the MHC class I antigen-processing pathway and also explains the paradox of why many MHC class I molecules display peptides with the X-P-Xn motif despite the inability of the transporter associated with antigen processing to transport such peptides from the cytoplasm.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aminopeptidases / metabolism*
  • Animals
  • Antigen Presentation / immunology*
  • CHO Cells
  • COS Cells
  • Chlorocebus aethiops
  • Cricetinae
  • Endoplasmic Reticulum / enzymology*
  • Histocompatibility Antigens Class I / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Microsomes
  • Peptides / immunology*
  • Proline


  • Histocompatibility Antigens Class I
  • Peptides
  • Proline
  • Aminopeptidases