An antigen produced by splicing of noncontiguous peptides in the reverse order

Science. 2006 Sep 8;313(5792):1444-7. doi: 10.1126/science.1130660.

Abstract

CD8-positive T lymphocytes recognize peptides that are usually derived from the degradation of cellular proteins and are presented by class I molecules of the major histocompatibility complex. Here we describe a human minor histocompatibility antigen created by a polymorphism in the SP110 nuclear phosphoprotein gene. The antigenic peptide comprises two noncontiguous SP110 peptide segments spliced together in reverse order to that in which they occur in the predicted SP110 protein. The antigenic peptide could be produced in vitro by incubation of precursor peptides with highly purified 20S proteasomes. Cutting and splicing probably occur within the proteasome by transpeptidation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Amino Acid Substitution
  • Antigen Presentation*
  • B-Lymphocytes / immunology
  • Cell Line, Transformed
  • Cytotoxicity, Immunologic
  • Electroporation
  • HLA-A Antigens / immunology
  • Humans
  • Interferon-gamma / metabolism
  • Male
  • Middle Aged
  • Minor Histocompatibility Antigens / genetics
  • Minor Histocompatibility Antigens / immunology*
  • Minor Histocompatibility Antigens / metabolism*
  • Molecular Sequence Data
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / genetics
  • Nuclear Proteins / immunology*
  • Nuclear Proteins / metabolism*
  • Peptide Fragments / metabolism
  • Polymorphism, Single Nucleotide
  • Proteasome Endopeptidase Complex / metabolism
  • Protein Splicing*
  • T-Lymphocytes, Cytotoxic / immunology*

Substances

  • HLA-A Antigens
  • Minor Histocompatibility Antigens
  • Nuclear Proteins
  • Peptide Fragments
  • Sp110 protein, human
  • Interferon-gamma
  • Proteasome Endopeptidase Complex