Cooperative Association of T Cell β 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 β 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 β 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.