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Constitutive Display of Cryptic Translation Products by MHC Class I Molecules
Susan R. Schwab,Katy C. Li,Chulho Kang,Nilabh Shastri*
Major histocompatibility complex (MHC) class I molecules displaytens of thousands of peptides on the cell surface, derived fromvirtually all endogenous proteins, for inspection by cytotoxicT cells (CTLs). We show that, in normal mouse cells, MHC I moleculespresent a peptide encoded in the 3' "untranslated" region. Despiteits rarity, the peptide elicits CTL responses and induces self-tolerance,establishing that immune surveillance extends well beyond conventionalpolypeptides. Furthermore, translation of this cryptic peptideoccurs by a previously unknown mechanism that decodes the CUGinitiation codon as leucine rather than the canonical methionine.
Division of Immunology, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720–3200, USA.
* To whom correspondence should be addressed. E-mail: nshastri{at}socrates.berkeley.edu
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Z. Xiong, E. Liu, Y. Yan, R. T. Silver, F. Yang, I. H. Chen, Y. Chen, S. Verstovsek, H. Wang, J. Prchal, et al. (2006)
J. Immunol.
177, 4907-4916
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Priming Protective CD8 T Cell Immunity by DNA Vaccines Encoding Chimeric, Stress Protein-Capturing Tumor-Associated Antigen.
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177, 1534-1542
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Epitopes Derived by Incidental Translational Frameshifting Give Rise to a Protective CTL Response..
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176, 6928-6934
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Effector-phase tolerance: another mechanism of how cancer escapes antitumor immune response.
HLA class I-restricted responses to vaccinia recognize a broad array of proteins mainly involved in virulence and viral gene regulation.
C. Oseroff, F. Kos, H.-H. Bui, B. Peters, V. Pasquetto, J. Glenn, T. Palmore, J. Sidney, D. C. Tscharke, J. R. Bennink, et al. (2005)
PNAS
102, 13980-13985
|Abstract »|Full Text »|PDF »
Translation from Cryptic Reading Frames of DNA Vaccines Generates an Extended Repertoire of Immunogenic, MHC Class I-Restricted Epitopes.
R. Schirmbeck, P. Riedl, N. Fissolo, F. A. Lemonnier, A. Bertoletti, and J. Reimann (2005)
J. Immunol.
174, 4647-4656
|Abstract »|Full Text »|PDF »
A Novel HLA-A*3303-Restricted Minor Histocompatibility Antigen Encoded by an Unconventional Open Reading Frame of Human TMSB4Y Gene.
H. Torikai, Y. Akatsuka, M. Miyazaki, E. H. Warren III, T. Oba, K. Tsujimura, K. Motoyoshi, Y. Morishima, Y. Kodera, K. Kuzushima, et al. (2004)
J. Immunol.
173, 7046-7054
|Abstract »|Full Text »|PDF »
Identification of Cryptic MHC I-restricted Epitopes Encoded by HIV-1 Alternative Reading Frames.
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J. Exp. Med.
199, 1053-1063
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Dendritic cell aggresome-like induced structures are dedicated areas for ubiquitination and storage of newly synthesized defective proteins.
H. Lelouard, V. Ferrand, D. Marguet, J. Bania, V. Camosseto, A. David, E. Gatti, and P. Pierre (2004)
J. Cell Biol.
164, 667-675
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J. Immunol.
172, 2944-2952
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