TY - JOUR
T1 - Discrete proteolytic intermediates in the MHC Class I antigen processing pathway and MHC I-dependent peptide trimming in the ER
AU - Paz, Pedro
AU - Brouwenstijn, Nathalie
AU - Perry, Robin
AU - Shastri, Nilabh
N1 - Funding Information:
We are grateful to Ms. Elsa Jimenez for assistance and Ms. Susan Schwab for careful reading of the manuscript. This research was supported by grants from the National Institutes of Health to N. S. and a postdoctoral fellowship from the Dutch Cancer Society to N. B.
PY - 1999/8
Y1 - 1999/8
N2 - The antigen processing pathway generates the peptides displayed by MHC I molecules on the cell surface. Whether these peptides are generated in the cytosol or from longer intermediates transported into the ER is unclear, because peptides other than those bound to MHC I have been difficult to find. Using a novel assay, we show that N-terminally extended antigenic analogs were associated with high-molecular weight material in the cytosol and were transported by TAP. In the ER, a nonapeptide was predominant that was converted to the final octapeptide only in presence of the appropriate MHC I molecule. The existence of extended peptides and their MHC I-dependent trimming suggest a mechanism for efficiently satisfying the distinct sequence preferences of polymorphic MHC I molecules.
AB - The antigen processing pathway generates the peptides displayed by MHC I molecules on the cell surface. Whether these peptides are generated in the cytosol or from longer intermediates transported into the ER is unclear, because peptides other than those bound to MHC I have been difficult to find. Using a novel assay, we show that N-terminally extended antigenic analogs were associated with high-molecular weight material in the cytosol and were transported by TAP. In the ER, a nonapeptide was predominant that was converted to the final octapeptide only in presence of the appropriate MHC I molecule. The existence of extended peptides and their MHC I-dependent trimming suggest a mechanism for efficiently satisfying the distinct sequence preferences of polymorphic MHC I molecules.
UR - http://www.scopus.com/inward/record.url?scp=0033179885&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033179885&partnerID=8YFLogxK
U2 - 10.1016/S1074-7613(00)80099-0
DO - 10.1016/S1074-7613(00)80099-0
M3 - Article
C2 - 10485659
AN - SCOPUS:0033179885
SN - 1074-7613
VL - 11
SP - 241
EP - 251
JO - Immunity
JF - Immunity
IS - 2
ER -