Double-stranded deoxyribonucleic acid binds to HLA class II molecules and inhibits HLA class II-mediated antigen presentation

Gilberto Filaci, Paola Contini, Iolanda Grasso, Donatella Bignardi, Massimo Ghio, Lorella Lanza, Marco Scudeletti, Francesco Puppo, Martine Bolognesi, Roberto S. Accolla, Francesco Indiveri

Research output: Contribution to journalArticlepeer-review

Abstract

CD4+ T cells proliferating in response to purified double-stranded deoxyribonucleic acid (dsDNA) have been recently demonstrated in peripheral blood mononuclear cells of patients with systemic lupus erythematosus. Their activation was inhibited by anti-HLA class II (HLA-II) monoclonal antibodies; thus, the existence of a molecular interaction between dsDNA and HL4-II is conceivable. In this report we show that dsDNA specifically bind to HLA-II. After preincubating cells with purified dsDNA or synthetic oligonucleotides, dsDNA was detected on the cell membrane and in the lysates of HLA-II+ but not of isogenic HLA-II- cell lines. We demonstrate that dsDNA binding inhibits that of a specific peptide to HLA-II. Mixed lymphocyte reaction and antigen-specific T cell proliferation were inhibited by the preincubation of stimulator cells or antigen-presenting cells with dsDNA. These results suggest the existence of a novel mechanism of down-modulation of the CD4+ T cell function generated by lack of stimulation due to the HLA-II presenting molecules being 'occupied' by dsDNA.

Original languageEnglish
Pages (from-to)3968-3979
Number of pages12
JournalEuropean Journal of Immunology
Volume28
Issue number12
Publication statusPublished - Dec 1998

Keywords

  • Antigen presentation
  • DNA
  • HLA class II molecule
  • Mixed leukocyte reaction
  • Tolerance

ASJC Scopus subject areas

  • Immunology

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