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Science 5 September 2003:
Vol. 301. no. 5638, pp. 1367 - 1371
DOI: 10.1126/science.1085650
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Reports
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 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.
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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