title: ER aminopeptidases generate a unique pool of peptides for MHC class I molecules.
abstract: 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.
authors: Division of Immunology, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3200, USA.
authors: T
authors: T
authors: Serwold
authors: S
authors: S
authors: Gaw
authors: N
authors: N
authors: Shastri
mesh_terms: D000626:Aminopeptidases / Q000378:metabolism*; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D016466:CHO Cells; D019556:COS Cells; D002522:Chlorocebus aethiops; D006224:Cricetinae; D004721:Endoplasmic Reticulum / Q000201:enzymology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008861:Microsomes; D010455:Peptides / Q000276:immunology*; D011392:Proline
chemical_list: D015395:Histocompatibility Antigens Class I; D010455:Peptides; D011392:Proline; D000626:Aminopeptidases