TY - JOUR
T1 - MHC class I molecules can direct proteolytic cleavage of antigenic precursors in the endoplasmic reticulum
AU - Brouwenstijn, Nathalie
AU - Serwold, Thomas
AU - Shastri, Nilabh
N1 - Funding Information:
We thank Susan Schwab for comments on the manuscript. This research was supported by grants from the National Institute of Health to N.S. N.B. was supported by the Dutch Cancer Society and by a postdoctoral fellowship award made possible by the Wheeler Fund for the Biological Sciences at the University of California Berkeley.
PY - 2001
Y1 - 2001
N2 - The large set of peptides presented by MHC (major histocompatibility complex) class I molecules are generated by proteolysis of diverse precursors in the cytoplasm and possibly in the endoplasmic reticulum (ER). To define the potential peptide trimming events in the ER, we analyzed proteolytic products generated in isolated microsomes. The residues flanking the N terminus of the final antigenic peptide were rapidly removed within the microsomes but only in the presence of appropriate MHC molecules. Remarkably, the precursor peptide was bound to the MHC molecules in a distinct conformation and required an aminopeptidase activity to generate the optimal peptide. The MHC molecules are therefore not only the final repositories of antigenic peptides, but they can also direct their excision from longer precursors.
AB - The large set of peptides presented by MHC (major histocompatibility complex) class I molecules are generated by proteolysis of diverse precursors in the cytoplasm and possibly in the endoplasmic reticulum (ER). To define the potential peptide trimming events in the ER, we analyzed proteolytic products generated in isolated microsomes. The residues flanking the N terminus of the final antigenic peptide were rapidly removed within the microsomes but only in the presence of appropriate MHC molecules. Remarkably, the precursor peptide was bound to the MHC molecules in a distinct conformation and required an aminopeptidase activity to generate the optimal peptide. The MHC molecules are therefore not only the final repositories of antigenic peptides, but they can also direct their excision from longer precursors.
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U2 - 10.1016/S1074-7613(01)00174-1
DO - 10.1016/S1074-7613(01)00174-1
M3 - Article
C2 - 11485741
AN - SCOPUS:0034907526
SN - 1074-7613
VL - 15
SP - 95
EP - 104
JO - Immunity
JF - Immunity
IS - 1
ER -