Double-stranded deoxyribonucleic acid binds to HLA class II molecules and inhibits HLA class II-mediated antigen presentation.
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 HLA-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.
Filaci
G
G
Department of Internal Medicine (DIMI), University of Genoa, Italy.
Contini
P
P
Grasso
I
I
Bignardi
D
D
Ghio
M
M
Lanza
L
L
Scudeletti
M
M
Puppo
F
F
Bolognesi
M
M
Accolla
R S
RS
Indiveri
F
F
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D004247:DNA / Q000235:genetics / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D009841:Oligonucleotides; D010455:Peptides; D011485:Protein Binding; D013601:T-Lymphocytes / Q000276:immunology*
D000949:Histocompatibility Antigens Class II; D009841:Oligonucleotides; D010455:Peptides; D004247:DNA