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 DQB10201 and one of DQA10101, DQA10102, or DQA10103 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.