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Constitutive Display of Cryptic Translation Products by MHC Class I Molecules

Science, 5 September 2003
Vol. 301, Issue 5638, p. 1367-1371
DOI: 10.1126/science.1085650

Constitutive Display of Cryptic Translation Products by MHC Class I Molecules

  1. Susan R. Schwab,
  2. Katy C. Li,
  3. Chulho Kang,
  4. Nilabh Shastri*
  1. Division of Immunology, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720–3200, USA.
  1. * To whom correspondence should be addressed. E-mail: nshastri{at}socrates.berkeley.edu

Abstract

Major histocompatibility complex (MHC) class I molecules display tens of thousands of peptides on the cell surface, derived from virtually all endogenous proteins, for inspection by cytotoxic T cells (CTLs). We show that, in normal mouse cells, MHC I molecules present a peptide encoded in the 3′ “untranslated” region. Despite its rarity, the peptide elicits CTL responses and induces self-tolerance, establishing that immune surveillance extends well beyond conventional polypeptides. Furthermore, translation of this cryptic peptide occurs by a previously unknown mechanism that decodes the CUG initiation codon as leucine rather than the canonical methionine.

  • Received for publication 14 April 2003.
  • Accepted for publication 21 July 2003.

Citation:

S. R. Schwab, K. C. Li, C. Kang, and N. Shastri, Constitutive Display of Cryptic Translation Products by MHC Class I Molecules. Science 301, 1367-1371 (2003).

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D. Bourdetsky, C. E. H. Schmelzer, and A. Admon
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Leucine-tRNA Initiates at CUG Start Codons for Protein Synthesis and Presentation by MHC Class I
S. R. Starck, V. Jiang, M. Pavon-Eternod, S. Prasad, B. McCarthy, T. Pan, and N. Shastri
Science 336, 1719-1723 (29 June 2012)

A New Start for Protein Synthesis
T. E. Dever, V. Jiang, M. Pavon-Eternod, S. Prasad, B. McCarthy, T. Pan, and N. Shastri
Science 336, 1645-1646 (29 June 2012)

Major source of antigenic peptides for the MHC class I pathway is produced during the pioneer round of mRNA translation
S. Apcher, C. Daskalogianni, F. Lejeune, B. Manoury, G. Imhoos, L. Heslop, and R. Fahraeus
Proc. Natl. Acad. Sci. USA 108, 11572-11577 (12 July 2011)

CD8 T cell response and evolutionary pressure to HIV-1 cryptic epitopes derived from antisense transcription
A. Bansal, J. Carlson, J. Yan, O. T. Akinsiku, M. Schaefer, S. Sabbaj, A. Bet, D. N. Levy, S. Heath, J. Tang et al.
JEM 207, 51-59 (18 January 2010)

Robust, Vaccine-Induced CD8+ T Lymphocyte Response against an Out-of-Frame Epitope
N. J. Maness, N. A. Wilson, J. S. Reed, S. M. Piaskowski, J. B. Sacha, A. D. Walsh, E. Thoryk, G. J. Heidecker, M. P. Citron, X. Liang et al.
J. Immunol. 184, 67-72 (1 January 2010)

Cellular immune response to cryptic epitopes during therapeutic gene transfer
C. Li, K. Goudy, M. Hirsch, A. Asokan, Y. Fan, J. Alexander, J. Sun, P. Monahan, D. Seiber, J. Sidney et al.
Proc. Natl. Acad. Sci. USA 106, 10770-10774 (30 June 2009)

Alternative Translational Products and Cryptic T Cell Epitopes: Expecting the Unexpected
O. Ho, and W. R. Green
J. Immunol. 177, 8283-8289 (15 December 2006)

An Unconventional Antigen Translated by a Novel Internal Ribosome Entry Site Elicits Antitumor Humoral Immune Reactions
Z. Xiong, E. Liu, Y. Yan, R. T. Silver, F. Yang, I. H. Chen, Y. Chen, S. Verstovsek, H. Wang, J. Prchal et al.
J. Immunol. 177, 4907-4916 (1 October 2006)

Priming Protective CD8 T Cell Immunity by DNA Vaccines Encoding Chimeric, Stress Protein-Capturing Tumor-Associated Antigen
R. Schirmbeck, P. Riedl, M. Kupferschmitt, U. Wegenka, H. Hauser, J. Rice, A. Kroger, and J. Reimann
J. Immunol. 177, 1534-1542 (1 August 2006)

Epitopes Derived by Incidental Translational Frameshifting Give Rise to a Protective CTL Response
M. B. Zook, M. T. Howard, G. Sinnathamby, J. F. Atkins, and L. C. Eisenlohr
J. Immunol. 176, 6928-6934 (1 June 2006)

Effector-phase tolerance: another mechanism of how cancer escapes antitumor immune response
A. B. Frey, and N. Monu
J. Leukoc. Biol. 79, 652-662 (1 April 2006)

Cytolytic CD8+ T Cells Directed against a Cryptic Epitope Derived from a Retroviral Alternative Reading Frame Confer Disease Protection
O. Ho, and W. R. Green
J. Immunol. 176, 2470-2475 (15 February 2006)

Physical and biochemical properties of mammalian DNase X proteins: non-AUG translation initiation of porcine and bovine mRNAs for DNase X
D. Shiokawa, Y. Shika, K. Saito, K. Yamazaki, and S.-i. Tanuma
Biochem. J. 392, 511-517 (15 December 2005)

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.
Proc. Natl. Acad. Sci. USA 102, 13980-13985 (27 September 2005)

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
J. Immunol. 174, 4647-4656 (15 April 2005)

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, T. Oba, K. Tsujimura, K. Motoyoshi, Y. Morishima, Y. Kodera, K. Kuzushima et al.
J. Immunol. 173, 7046-7054 (1 December 2004)

CELL BIOLOGY: Cutting and Pasting Antigenic Peptides
P. Cresswell, Y. Akatsuka, M. Miyazaki, E. H. Warren, T. Oba, K. Tsujimura, K. Motoyoshi, Y. Morishima, Y. Kodera, K. Kuzushima et al.
Science 304, 525-527 (23 April 2004)

Identification of Cryptic MHC I-restricted Epitopes Encoded by HIV-1 Alternative Reading Frames
S. Cardinaud, A. Moris, M. Fevrier, P.-S. Rohrlich, L. Weiss, P. Langlade-Demoyen, F. A. Lemonnier, O. Schwartz, and A. Habel
JEM 199, 1053-1063 (19 April 2004)

Toward a Definition of Self: Proteomic Evaluation of the Class I Peptide Repertoire
H. D. Hickman, A. D. Luis, R. Buchli, S. R. Few, M. Sathiamurthy, R. S. VanGundy, C. F. Giberson, and W. H. Hildebrand
J. Immunol. 172, 2944-2952 (1 March 2004)

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
JCB 164, 667-675 (1 March 2004)

IMMUNOLOGY: Hide and Seek in the Peptidome
J. W. Yewdell, V. Ferrand, D. Marguet, J. Bania, V. Camosseto, A. David, E. Gatti, and P. Pierre
Science 301, 1334-1335 (5 September 2003)

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