Suppression by mAbs against DQB1 peptides of in vitro proliferation of AChR-specific T cells from myasthenia gravis patients.
It has been indicated that multiple genes, including HLA genes, are collectively involved in the susceptibility to myasthenia gravis (MG). DQB1 alleles represent one of those associated with MG. We have prepared B-cell hybridomas that produce mAbs against peptides corresponding to the tip of the MHC antigen-binding cavity (region 70-90) of alleles DQB1*02, *03, *05 and *06. The mAbs bound to DQ molecules isolated from cells. In the assays using peripheral blood lymphocytes (PBL) from patients with MG, the mAbs against peptides of the correlate HLA DQ sequences inhibited the in vitro proliferation of acetylcholine receptor (AChR)-specific T cells. The results indicate that the function of disease-related MHC alleles may be blocked by directly and selectively targeting the antigen-presenting region on these MHC molecules. The results also suggest that DQ molecules are one of those involved in the restriction of autoimmune anti-AChR responses in MG. The strategy could provide an effective means for immunointervention in MG. It may also potentially be adapted for down-regulation of undesirable immune responses such as in other autoimmune diseases, allergic reactions, or clinical conditions where immune responses to a therapeutic protein develop.
Oshima
Minako
M
Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA. moshima@bcm.tmc.edu
Ohtani
Maki
M
Deitiker
Philip R
PR
Smith
R Glenn
RG
Mosier
Dennis R
DR
Atassi
M Zouhair
MZ
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D005260:Female; D006683:HLA-DQ Antigens / Q000276:immunology*; D059866:HLA-DQ beta-Chains; D006801:Humans; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000188:drug therapy / Q000276:immunology*; D011950:Receptors, Cholinergic / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D011950:Receptors, Cholinergic