Trimming of antigenic peptides in an early secretory compartment

doi:10.1084/jem.180.6.2389

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Trimming of antigenic peptides in an early secretory compartment

HL Snyder, JW Yewdell and JR Bennink
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.

Major histocompatibility complex (MHC) class I molecules bind peptides of 8-10 residues in the endoplasmic reticulum (ER) and convey them to the cell surface for inspection by CD8-expressing T cells (TCD8+). Antigenic peptides are predominantly derived from a cytosolic pool of polypeptides. The proteolytic generation of peptides from polypeptides clearly begins in the cytosol, but it is uncertain whether the final proteolytic steps occur before or after peptides are transported into the ER by the MHC-encoded peptide transporter (TAP). To study the trimming of antigenic peptides in the secretory pathway in the absence of cytosolic processing, we used an NH2-terminal signal sequence to target to the ER of TAP-deficient cells, "tandem" peptides consisting of two defined TCD8+ determinants arranged from head to tail. We find that in contrast to cytosolic proteases in TAP-expressing cells, which are able to liberate antigenic peptides from either end of a tandem peptide, proteases (probably aminopeptidases) present in an early secretory compartment preferentially liberate the COOH-terminal determinant. These findings demonstrate that proteolytic activities associated with antigen processing are not limited to the cytosol, but that they also exist in an early secretory compartment. Such secretory aminopeptidases may function to trim TAP-transported peptides to the optimal size for binding to class I molecules.
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Theobald, M., Ruppert, T., Kuckelkorn, U., Hernandez, J., Haussler, A., Ferreira, E. A., Liewer, U., Biggs, J., Levine, A. J., Huber, C., Koszinowski, U. H., Kloetzel, P.-M., Sherman, L. A. (1998). The Sequence Alteration Associated with a Mutational Hotspot in p53 Protects Cells From Lysis by Cytotoxic T Lymphocytes Specific for a Flanking Peptide Epitope. JEM 188: 1017-1028 [Abstract] [Full Text]
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Deng, Y., Gibbs, J., Bacik, I., Porgador, A., Copeman, J., Lehner, P., Ortmann, B., Cresswell, P., Bennink, J. R., Yewdell, J. W. (1998). Assembly of MHC Class I Molecules with Biosynthesized Endoplasmic Reticulum-Targeted Peptides Is Inefficient in Insect Cells and Can Be Enhanced by Protease Inhibitors. J. Immunol. 161: 1677-1685 [Abstract] [Full Text]
Beninga, J., Rock, K. L., Goldberg, A. L. (1998). Interferon-gamma Can Stimulate Post-proteasomal Trimming of the N Terminus of an Antigenic Peptide by Inducing Leucine Aminopeptidase. J. Biol. Chem. 273: 18734-18742 [Abstract] [Full Text]
Daniel, S., Brusic, V., Caillat-Zucman, S., Petrovsky, N., Harrison, L., Riganelli, D., Sinigaglia, F., Gallazzi, F., Hammer, J., van Endert, P. M. (1998). Relationship Between Peptide Selectivities of Human Transporters Associated with Antigen Processing and HLA Class I Molecules. J. Immunol. 161: 617-624 [Abstract] [Full Text]
Luckey, C. J., King, G. M., Marto, J. A., Venketeswaran, S., Maier, B. F., Crotzer, V. L., Colella, T. A., Shabanowitz, J., Hunt, D. F., Engelhard, V. H. (1998). Proteasomes Can Either Generate or Destroy MHC Class I Epitopes: Evidence for Nonproteasomal Epitope Generation in the Cytosol. J. Immunol. 161: 112-121 [Abstract] [Full Text]
Anton, L. C., Snyder, H. L., Bennink, J. R., Vinitsky, A., Orlowski, M., Porgador, A., Yewdell, J. W. (1998). Dissociation of Proteasomal Degradation of Biosynthesized Viral Proteins from Generation of MHC Class I-Associated Antigenic Peptides. J. Immunol. 160: 4859-4868 [Abstract] [Full Text]
Vijh, S., Pilip, I. M., Pamer, E. G. (1998). Effect of Antigen-Processing Efficiency on In Vivo T Cell Response Magnitudes. J. Immunol. 160: 3971-3977 [Abstract] [Full Text]
Fu, T.-M., Mylin, L. M., Schell, T. D., Bacik, I., Russ, G., Yewdell, J. W., Bennink, J. R., Tevethia, S. S. (1998). An Endoplasmic Reticulum-Targeting Signal Sequence Enhances the Immunogenicity of an Immunorecessive Simian Virus 40�Large T Antigen Cytotoxic T-Lymphocyte Epitope. J. Virol. 72: 1469-1481 [Abstract] [Full Text]
Mosse, C. A., Meadows, L., Luckey, C. J., Kittlesen, D. J., Huczko, E. L., Slingluff, C. L. Jr., Shabanowitz, J., Hunt, D. F., Engelhard, V. H. (1998). The Class I Antigen-processing Pathway for the Membrane Protein Tyrosinase Involves Translation in the Endoplasmic Reticulum and Processing in the Cytosol. JEM 187: 37-48 [Abstract] [Full Text]
Snyder, H. L., Bacik, I., Bennink, J. R., Kearns, G., Behrens, T. W., Bachi, T., Orlowski, M., Yewdell, J. W. (1997). Two Novel Routes of Transporter Associated with Antigen Processing (TAP)-independent Major Histocompatibility Complex Class I Antigen Processing. JEM 186: 1087-1098 [Abstract] [Full Text]
Craiu, A., Akopian, T., Goldberg, A., Rock, K. L. (1997). Two distinct proteolytic processes in the generation of a major histocompatibility complex class I-presented�peptide. Proc. Natl. Acad. Sci. USA 94: 10850-10855 [Abstract] [Full Text]
Bacik, I., Snyder, H. L., Anton, L. C., Russ, G., Chen, W., Bennink, J. R., Urge, L., Otvos, L., Dudkowska, B., Eisenlohr, L., Yewdell, J. W. (1997). Introduction of a Glycosylation Site into a Secreted Protein Provides Evidence for an Alternative Antigen Processing Pathway: Transport of Precursors of Major Histocompatability Complex Class I-Restricted Peptides from the Endoplasmic Reticulum to the Cytosol. JEM 186: 479-487 [Abstract] [Full Text]
Day, P. M., Yewdell, J. W., Porgador, A., Germain, R. N., Bennink, J. R. (1997). Direct delivery of exogenous MHC class I molecule-binding oligopeptides to the endoplasmic reticulum of viable�cells. Proc. Natl. Acad. Sci. USA 94: 8064-8069 [Abstract] [Full Text]
Malarkannan, S., Serwold, T., Nguyen, V., Sherman, L.�A., Shastri, N. (1996). The mouse mammary tumor virus env gene is the source of a CD8+ T-cell-stimulating peptide presented by a major histocompatibility complex class I molecule in a murine�thymoma. Proc. Natl. Acad. Sci. USA 93: 13991-13996 [Abstract] [Full Text]
Goldberg, A.L., Gaczynska, M., Grant, E., Michalek, M., Rock, K.L. (1995). Functions of the Proteasome in Antigen Presentation. Cold Spring Harb Symp Quant Biol 60: 479-490 [Abstract]
Komlosh, A., Momburg, F., Weinschenk, T., Emmerich, N., Schild, H., Nadav, E., Shaked, I., Reiss, Y. (2001). A Role for a Novel Luminal Endoplasmic Reticulum Aminopeptidase in Final Trimming of 26 S Proteasome-generated Major Histocompatability Complex Class I Antigenic Peptides. J. Biol. Chem. 276: 30050-30056 [Abstract] [Full Text]
Menoret, A., Li, Z., Niswonger, M. L., Altmeyer, A., Srivastava, P. K. (2001). An Endoplasmic Reticulum Protein Implicated in Chaperoning Peptides to Major Histocompatibility of Class I Is an Aminopeptidase. J. Biol. Chem. 276: 33313-33318 [Abstract] [Full Text]
Alvarez, I., Sesma, L., Marcilla, M., Ramos, M., Marti, M., Camafeita, E., de Castro, J. A. L. (2001). Identification of Novel HLA-B27 Ligands Derived from Polymorphic Regions of Its Own or Other Class I Molecules Based on Direct Generation by 20 S Proteasome. J. Biol. Chem. 276: 32729-32737 [Abstract] [Full Text]
Hudrisier, D., Riond, J., Mazarguil, H., Gairin, J. E. (2001). Pleiotropic Effects of Post-translational Modifications on the Fate of Viral Glycopeptides as Cytotoxic T Cell Epitopes. J. Biol. Chem. 276: 38255-38260 [Abstract] [Full Text]