TY - JOUR
T1 - Endoplasmic reticulum aminopeptidase associated with antigen processing regulates quality of processed peptides presented by MHC class I molecules
AU - Kanaseki, Takayuki
AU - Shastri, Nilabh
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2008/11/1
Y1 - 2008/11/1
N2 - Effective immune surveillance by CD8 T cells depends on the presentation of diverse peptides by MHC class I (pMHC I) molecules on the cell surface. The pMHC I repertoire is shaped in the endoplasmic reticulum (ER) by the ER aminopeptidase associated with Ag processing (ERAAP). The ERAAP activity is required for producing peptides of appropriate length for generating optimal pMHC I. Paradoxically, ERAAP also inhibits generation of certain peptides such as the SVL9 (SSVVGVWYL) peptide encoded by the H13a histocompatibility gene and presented by Db MHC by an unknown mechanism. In this study, we show that the presentation of the SVL9-D b complex is inhibited when other peptides compete for binding D b. Conversely, improving the binding of SVL9 peptide to Db suppresses the inhibition. Interestingly, the inhibitory effect of competitor peptides is observed only when ERAAP is expressed in the same cells. Thus, ERAAP, in concert with MHC I molecules, regulates the quality of processed peptides presented on the cell surface.
AB - Effective immune surveillance by CD8 T cells depends on the presentation of diverse peptides by MHC class I (pMHC I) molecules on the cell surface. The pMHC I repertoire is shaped in the endoplasmic reticulum (ER) by the ER aminopeptidase associated with Ag processing (ERAAP). The ERAAP activity is required for producing peptides of appropriate length for generating optimal pMHC I. Paradoxically, ERAAP also inhibits generation of certain peptides such as the SVL9 (SSVVGVWYL) peptide encoded by the H13a histocompatibility gene and presented by Db MHC by an unknown mechanism. In this study, we show that the presentation of the SVL9-D b complex is inhibited when other peptides compete for binding D b. Conversely, improving the binding of SVL9 peptide to Db suppresses the inhibition. Interestingly, the inhibitory effect of competitor peptides is observed only when ERAAP is expressed in the same cells. Thus, ERAAP, in concert with MHC I molecules, regulates the quality of processed peptides presented on the cell surface.
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U2 - 10.4049/jimmunol.181.9.6275
DO - 10.4049/jimmunol.181.9.6275
M3 - Article
C2 - 18941218
AN - SCOPUS:58749092174
SN - 0022-1767
VL - 181
SP - 6275
EP - 6282
JO - Journal of Immunology
JF - Journal of Immunology
IS - 9
ER -