Constitutive Display of Cryptic Translation Products by MHC Class I Molecules

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Science  05 Sep 2003:
Vol. 301, Issue 5638, pp. 1367-1371
DOI: 10.1126/science.1085650

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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.

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