Major histocompatibility class I molecules can present cryptic translation products to T-cells

N. Shastri, V. Nguyen, F. Gonzalez

Research output: Contribution to journalArticle

Abstract

Self or foreign cellular proteins provide peptides for presentation by major histocompatibility complex (MHC) class I molecules on the surface of antigen presenting cells (APC). Surprisingly, several studies have shown that T-cells can recognize APC transfected with antigen genes that were not present in the appropriate translational context. To understand the basis of this phenomenon, APC were transfected with DNA constructs encoding the OVA257-264 (SL8) peptide, but with varying translation initiation codons. We report that, in addition to ATG, 6 other codons (ATT, ACG, CTG, GCG, TGG, GAT) also allowed presentation to SL8·Kb-specific T-cells. Significantly, this set includes 3 of 4 known non-ATG translation initiation codons strongly suggesting that cryptic translation accounts for this phenomenon. Although expression of the SL8·Kb complex was readily detected by T-cell activation, the amount of processed peptides was below detection limit (<30 copies/cell) in cell extracts. Thus, the fortuitous presence of these cryptic translation initiation sites in transcribed genes can explain how peptide MHC complexes were obtained in sufficient amounts for T-cell activation. The translation initiation codons identified here could also be useful for identifying potential open reading frames that possess biological and/or immunological activities.

Original languageEnglish (US)
Pages (from-to)1088-1091
Number of pages4
JournalJournal of Biological Chemistry
Volume270
Issue number3
DOIs
StatePublished - Jan 1 1995

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this