Constitutive display of cryptic translation products by MHC class I molecules.
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.
Schwab
Susan R
SR
Division of Immunology, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3200, USA.
Li
Katy C
KC
Kang
Chulho
C
Shastri
Nilabh
N
D020413:3' Untranslated Regions; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D001402:B-Lymphocytes / Q000378:metabolism; D001483:Base Sequence; D018387:Codon, Initiator; D018388:Codon, Terminator; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006183:H-2 Antigens / Q000276:immunology*; D006825:Hybridomas; D007930:Leucine / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D015778:Minor Histocompatibility Antigens / Q000235:genetics; D008969:Molecular Sequence Data; D010455:Peptides / Q000235:genetics* / Q000276:immunology*; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D017634:Self Tolerance; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection; D019076:Transgenes
D020413:3' Untranslated Regions; D018387:Codon, Initiator; D018388:Codon, Terminator; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D015778:Minor Histocompatibility Antigens; D010455:Peptides; D011506:Proteins; C102450:Uty protein, mouse; C114735:minor H antigen H60; D007930:Leucine