The JI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 QUICK SEARCH:   [advanced]


     
 


This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Serwold, T.
Right arrow Articles by Shastri, N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Serwold, T.
Right arrow Articles by Shastri, N.
Right arrowPubmed/NCBI databases
*Substance via MeSH
The Journal of Immunology, 1999, 162: 4712-4719.
Copyright © 1999 by The American Association of Immunologists

Specific Proteolytic Cleavages Limit the Diversity of the Pool of Peptides Available to MHC Class I Molecules in Living Cells1

Thomas Serwold and Nilabh Shastri2

Division of Immunology, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720

MHC class I molecules display peptides selected from a poorly characterized pool of peptides available in the endoplasmic reticulum. We analyzed the diversity of peptides available to MHC class I molecules by monitoring the generation of an OVA-derived octapeptide, OVA257–264 (SL8), and its C-terminally extended analog, SL8-I. The poorly antigenic SL8-I could be detected in cell extracts only after its conversion to the readily detectable SL8 with carboxypeptidase Y. Analysis of extracts from cells expressing the minimal precursor Met-SL8-I by this method revealed the presence of SL8/Kb and the extended SL8-I/Kb complexes, indicating that the peptide pool contained both peptides. In contrast, cells expressing full length OVA generated only the SL8/Kb complex, demonstrating that the peptide pool generated from the full length precursor contained only a subset of potential MHC-binding peptides. Deletion analysis revealed that SL8-I was generated only from precursors lacking additional C-terminal flanking residues, suggesting that the generation of the C terminus of the SL8 peptide involves a specific endopeptidase cleavage. To investigate the protease responsible for this cleavage, we tested the effect of different protease inhibitors on the generation of the SL8 and SL8-I peptides. Only the proteasome inhibitors blocked generation of SL8, but not SL8-I. These findings demonstrate that the specificities of the proteases in the Ag-processing pathway, which include but are not limited to the proteasome, limit the diversity of peptides available for binding by MHC class I molecules in the endoplasmic reticulum.




This article has been cited by other articles:


Home page
Proc. Natl. Acad. Sci. USAHome page
M. K. Callahan, M. Garg, and P. K. Srivastava
Heat-shock protein 90 associates with N-terminal extended peptides and is required for direct and indirect antigen presentation
PNAS, February 5, 2008; 105(5): 1662 - 1667.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
N. Tiwari, N. Garbi, T. Reinheckel, G. Moldenhauer, G. J. Hammerling, and F. Momburg
A Transporter Associated with Antigen-Processing Independent Vacuolar Pathway for the MHC Class I-Mediated Presentation of Endogenous Transmembrane Proteins
J. Immunol., June 15, 2007; 178(12): 7932 - 7942.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
Y. Samino, D. Lopez, S. Guil, L. Saveanu, P. M. van Endert, and M. Del Val
A Long N-terminal-extended Nested Set of Abundant and Antigenic Major Histocompatibility Complex Class I Natural Ligands from HIV Envelope Protein
J. Biol. Chem., March 10, 2006; 281(10): 6358 - 6365.
[Abstract] [Full Text] [PDF]


Home page
JEMHome page
R. Draenert, S. Le Gall, K. J. Pfafferott, A. J. Leslie, P. Chetty, C. Brander, E. C. Holmes, S.-C. Chang, M. E. Feeney, M. M. Addo, et al.
Immune Selection for Altered Antigen Processing Leads to Cytotoxic T Lymphocyte Escape in Chronic HIV-1 Infection
J. Exp. Med., April 5, 2004; 199(7): 905 - 915.
[Abstract] [Full Text] [PDF]


Home page
Mol. Cell. ProteomicsHome page
A. Admon, E. Barnea, and T. Ziv
Tumor Antigens and Proteomics from the Point of View of the Major Histocompatibility Complex Peptides
Mol. Cell. Proteomics, June 1, 2003; 2(6): 388 - 398.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
D. J. Campbell, T. Serwold, and N. Shastri
Bacterial Proteins Can Be Processed by Macrophages in a Transporter Associated with Antigen Processing-Independent, Cysteine Protease-Dependent Manner for Presentation by MHC Class I Molecules
J. Immunol., January 1, 2000; 164(1): 168 - 175.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
A. Paradela, I. Alvarez, M. Garcia-Peydro, L. Sesma, M. Ramos, J. Vazquez, and J. A. Lopez de Castro
Limited Diversity of Peptides Related to an Alloreactive T Cell Epitope in the HLA-B27-Bound Peptide Repertoire Results from Restrictions at Multiple Steps Along the Processing-Loading Pathway
J. Immunol., January 1, 2000; 164(1): 329 - 337.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 1999 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 1999 by The American Association of Immunologists, Inc. All rights reserved.