Double-stranded deoxyribonucleic acid binds to HLA class II molecules and inhibits HLA class II-mediated antigen presentation.
Eur J Immunol
; 28(12): 3968-79, 1998 12.
Article
in En
| MEDLINE
| ID: mdl-9862333
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 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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
DNA
/
T-Lymphocytes
/
Histocompatibility Antigens Class II
/
Antigen Presentation
Limits:
Animals
/
Humans
Language:
En
Journal:
Eur J Immunol
Year:
1998
Document type:
Article
Affiliation country:
Italy