TY - JOUR
T1 - Endoplasmic reticulum aminopeptidase associated with antigen processing defines the composition and structure of MHC class I peptide repertoire in normal and virus-infected cells
AU - Blanchard, Nicolas
AU - Kanaseki, Takayuki
AU - Escobar, Hernando
AU - Delebecque, Frédéric
AU - Nagarajan, Niranjana A.
AU - Reyes-Vargas, Eduardo
AU - Crockett, David K.
AU - Raulet, David H.
AU - Delgado, Julio C.
AU - Shastri, Nilabh
PY - 2010/3/15
Y1 - 2010/3/15
N2 - The MHC class I (MHC-I) molecules ferry a cargo of peptides to the cell surface as potential ligands for CD8+ cytotoxic T cells. For nearly 20 years, the cargo has been described as a collection of short 8-9 mer peptides, whose length and sequences were believed to be primarily determined by the peptide-binding groove of MHC-I molecules. Yet the mechanisms for producing peptides of such optimal length and composition have remained unclear. In this study, using mass spectrometry, we determined the amino acid sequences of a large number of naturally processed peptides in mice lacking the endoplasmic reticulum aminopeptidase associated with Ag processing (ERAAP). We find that ERAAP-deficiency changed the oeuvre and caused a marked increase in the length of peptides normally presented by MHC-I. Furthermore, we observed similar changes in the length of viral peptides recognized by CD8+ T cells in mouse CMV-infected ERAAP-deficient mice. In these mice, a distinct CD8 + T cell population was elicited with specificity for an N-terminally extended epitope. Thus, the characteristic length, as well as the composition of MHC-I peptide cargo, is determined not only by the MHC-I peptide-binding groove but also by ERAAP proteolysis in the endoplasmic reticulum.
AB - The MHC class I (MHC-I) molecules ferry a cargo of peptides to the cell surface as potential ligands for CD8+ cytotoxic T cells. For nearly 20 years, the cargo has been described as a collection of short 8-9 mer peptides, whose length and sequences were believed to be primarily determined by the peptide-binding groove of MHC-I molecules. Yet the mechanisms for producing peptides of such optimal length and composition have remained unclear. In this study, using mass spectrometry, we determined the amino acid sequences of a large number of naturally processed peptides in mice lacking the endoplasmic reticulum aminopeptidase associated with Ag processing (ERAAP). We find that ERAAP-deficiency changed the oeuvre and caused a marked increase in the length of peptides normally presented by MHC-I. Furthermore, we observed similar changes in the length of viral peptides recognized by CD8+ T cells in mouse CMV-infected ERAAP-deficient mice. In these mice, a distinct CD8 + T cell population was elicited with specificity for an N-terminally extended epitope. Thus, the characteristic length, as well as the composition of MHC-I peptide cargo, is determined not only by the MHC-I peptide-binding groove but also by ERAAP proteolysis in the endoplasmic reticulum.
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U2 - 10.4049/jimmunol.0903712
DO - 10.4049/jimmunol.0903712
M3 - Article
C2 - 20173027
AN - SCOPUS:77951900588
SN - 0022-1767
VL - 184
SP - 3033
EP - 3042
JO - Journal of Immunology
JF - Journal of Immunology
IS - 6
ER -