Contribution of Proteasome-Mediated Proteolysis to the Hierarchy of Epitopes Presented by Major Histocompatibility Complex Class I Molecules

Immunity. 1995 Mar;2(3):289-99. doi: 10.1016/1074-7613(95)90053-5.

Abstract

Major histocompatibility complex (MHC) class I-restricted cytotoxic T lymphocytes (CTL) recognize peptide epitopes of protein antigens in a hierarchical fashion. We investigated whether proteolytic cleavage, in particular by proteasomes, is important in determining epitope hierarchy. Using highly purified 20S proteasomes, we find preferred cleavage sites directly adjacent to the N- and C-terminal ends of the immunodominant epitope of chicken ovalbumin, Ova257-264, while most of the subdominant epitope, Ova55-62, is destroyed by a major cleavage site located within this epitope. Moreover, we show that variations in amino acid sequences flanking these epitopes influence proteasomal cleavage patterns in parallel with the efficacy of their presentation. The results suggest that proteasomal cleavage within and adjacent to class I-restricted epitopes contributes to their level of presentation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigen Presentation / immunology*
  • Cells, Cultured
  • Cysteine Endopeptidases / metabolism*
  • Cytotoxicity Tests, Immunologic / methods
  • Epitopes / immunology*
  • Epitopes / metabolism*
  • H-2 Antigens / genetics
  • Immunodominant Epitopes / immunology
  • Immunodominant Epitopes / metabolism
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Confocal
  • Molecular Sequence Data
  • Multienzyme Complexes / metabolism*
  • Ovalbumin / immunology
  • Ovalbumin / metabolism
  • Peptide Fragments / metabolism
  • Proteasome Endopeptidase Complex

Substances

  • Epitopes
  • H-2 Antigens
  • Immunodominant Epitopes
  • Multienzyme Complexes
  • Peptide Fragments
  • Ovalbumin
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex