Cooperative association of T cell beta receptor and HLA-DQ alleles in the production of anti-Ro in systemic lupus erythematosus.
The immunogenetics of the autoantibody response to Ro (or SS-A) have been explored in patients with systemic lupus erythematous. Data show that alleles of the T cell beta receptor and HLA-DQ loci are cooperatively associated with the presence of anti-Ro autoantibodies in systemic lupus erythematosus. Identification of HLA-DQ by oligonucleotide probe binding to polymerase chain reaction products demonstrates that the combination of DQB1*0201 and one of DQA1*0101, DQA1*0102, or DQA1*0103 is associated with anti-Ro. Patients possessing a particular pair of T cell receptor beta restriction enzyme polymorphisms along with these specific HLA-DQ alleles produce quantitatively more anti-Ro as measured by a sensitive solid-phase immunoassay than patients without these T cell receptor and DQ alleles. Other work has shown that the autoimmune response is directed against the human Ro antigen. These results are consistent with a central role in the disregulation of autoimmunity involving a trimolecular complex composed of the autoantigen bound by a HLA-DQ molecule which, together, are bound in turn by T cells which express a particular subset of T cell receptors.
Scofield
R H
RH
Arthritis and Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City.
Frank
M B
MB
Neas
B R
BR
Horowitz
R M
RM
Hardgrave
K L
KL
Fujisaku
A
A
McArthur
R
R
Harley
J B
JB
D000483:Alleles; D000974:Antibodies, Antinuclear / Q000096:biosynthesis*; D001324:Autoantigens / Q000276:immunology*; D015139:Blotting, Southern; D006683:HLA-DQ Antigens / Q000235:genetics*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology*; D012150:Polymorphism, Restriction Fragment Length; D020733:RNA, Small Cytoplasmic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D012261:Ribonucleoproteins / Q000276:immunology*; D000099207:SS-A Antigen
D000974:Antibodies, Antinuclear; D001324:Autoantigens; D006683:HLA-DQ Antigens; D020733:RNA, Small Cytoplasmic; D016693:Receptors, Antigen, T-Cell, alpha-beta; D012261:Ribonucleoproteins; D000099207:SS-A Antigen; C116006:RO60 protein, human; C035356:SS-A antibodies