TY - JOUR
T1 - Presentation without proteolytic cleavage of endogenous precursors in the MHC class I antigen processing pathway
AU - Buchholz, Daniel
AU - Scott, Paul
AU - Shastri, Nilabh
N1 - Copyright:
Copyright 2004 Elsevier B.V., All rights reserved.
PY - 1995/3/24
Y1 - 1995/3/24
N2 - The antigen presentation pathway yields peptide-MHC class I complexes on the antigen presenting cell (APC) surface for recognition by appropriate T- cells. Expression of the peptide-MHC complex on APC surface is preceded by several steps that include the generation of peptide fragments in the cytoplasm and their assembly with MHC molecules in the endoplasmic reticulum. It is now clear that MHC binding to optimally processed peptides in the endoplasmic reticulum is obligatory for their stable expression on the cell surface. However, whether a similar obligatory relationship exists between generation of processed peptides and their expression as peptide-MHC on APC surface is not known. Here, we addressed this question by analyzing the processing of ovalbumin (aa257-264, SL8) or influenza nucleoprotein (aa366- 374, AM9) analogs. We examined the generation of naturally processed peptides using precursors that did, or did not, contain residues flanking the optimal MHC-binding peptides. By characterizing the peptides generated from these precursors by T-cell stimulation assays and by high performance liquid chromatography analysis, we established that intracellular assembly of peptide-MHC complexes and their expression on the cell surface can occur with peptides that lack flanking residues. The presentation of these endogenously synthesized perfect fit peptides demonstrates that the cleavage of precursor polypeptides is an independent step in the antigen presentation pathway.
AB - The antigen presentation pathway yields peptide-MHC class I complexes on the antigen presenting cell (APC) surface for recognition by appropriate T- cells. Expression of the peptide-MHC complex on APC surface is preceded by several steps that include the generation of peptide fragments in the cytoplasm and their assembly with MHC molecules in the endoplasmic reticulum. It is now clear that MHC binding to optimally processed peptides in the endoplasmic reticulum is obligatory for their stable expression on the cell surface. However, whether a similar obligatory relationship exists between generation of processed peptides and their expression as peptide-MHC on APC surface is not known. Here, we addressed this question by analyzing the processing of ovalbumin (aa257-264, SL8) or influenza nucleoprotein (aa366- 374, AM9) analogs. We examined the generation of naturally processed peptides using precursors that did, or did not, contain residues flanking the optimal MHC-binding peptides. By characterizing the peptides generated from these precursors by T-cell stimulation assays and by high performance liquid chromatography analysis, we established that intracellular assembly of peptide-MHC complexes and their expression on the cell surface can occur with peptides that lack flanking residues. The presentation of these endogenously synthesized perfect fit peptides demonstrates that the cleavage of precursor polypeptides is an independent step in the antigen presentation pathway.
UR - http://www.scopus.com/inward/record.url?scp=0028941532&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028941532&partnerID=8YFLogxK
U2 - 10.1074/jbc.270.12.6515
DO - 10.1074/jbc.270.12.6515
M3 - Article
C2 - 7896786
AN - SCOPUS:0028941532
SN - 0021-9258
VL - 270
SP - 6515
EP - 6522
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 12
ER -