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 journalArticle

11 Citations (Scopus)

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

Fingerprint

Histocompatibility Antigens Class II
Antigen Presentation
HLA Antigens
DNA
T-Lymphocytes
Mixed Lymphocyte Culture Test
Antigen-Presenting Cells
Oligonucleotides
Systemic Lupus Erythematosus
Blood Cells
Monoclonal Antibodies
Cell Proliferation
Cell Membrane
Antigens
Cell Line
Peptides

Keywords

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

ASJC Scopus subject areas

  • Immunology

Cite this

Filaci, G., Contini, P., Grasso, I., Bignardi, D., Ghio, M., Lanza, L., ... Indiveri, F. (1998). Double-stranded deoxyribonucleic acid binds to HLA class II molecules and inhibits HLA class II-mediated antigen presentation. European Journal of Immunology, 28(12), 3968-3979.

Double-stranded deoxyribonucleic acid binds to HLA class II molecules and inhibits HLA class II-mediated antigen presentation. / Filaci, Gilberto; Contini, Paola; Grasso, Iolanda; Bignardi, Donatella; Ghio, Massimo; Lanza, Lorella; Scudeletti, Marco; Puppo, Francesco; Bolognesi, Martine; Accolla, Roberto S.; Indiveri, Francesco.

In: European Journal of Immunology, Vol. 28, No. 12, 12.1998, p. 3968-3979.

Research output: Contribution to journalArticle

Filaci, G, Contini, P, Grasso, I, Bignardi, D, Ghio, M, Lanza, L, Scudeletti, M, Puppo, F, Bolognesi, M, Accolla, RS & Indiveri, F 1998, 'Double-stranded deoxyribonucleic acid binds to HLA class II molecules and inhibits HLA class II-mediated antigen presentation', European Journal of Immunology, vol. 28, no. 12, pp. 3968-3979.
Filaci, Gilberto ; Contini, Paola ; Grasso, Iolanda ; Bignardi, Donatella ; Ghio, Massimo ; Lanza, Lorella ; Scudeletti, Marco ; Puppo, Francesco ; Bolognesi, Martine ; Accolla, Roberto S. ; Indiveri, Francesco. / Double-stranded deoxyribonucleic acid binds to HLA class II molecules and inhibits HLA class II-mediated antigen presentation. In: European Journal of Immunology. 1998 ; Vol. 28, No. 12. pp. 3968-3979.
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