Immunogenetics of epitopes of the carboxyl terminus of the human 60-kD Ro autoantigen.

Systemic lupus erythematosus is associated with the presence of autoantibodies which bind several ribonucleoproteins, including Ro (or SS-A). We have explored the relationship of the HLA-DQ and T cell receptor alleles in patients producing autoantibodies binding the 13-kD carboxyl terminus fragment of the 60-kD Ro and with autoantibodies binding a peptide epitope within this fragment (amino acid residues 480-494). Antibodies binding the 13-kD fragment are more likely to be found in the sera of patients with particular DQA1 and DQB1 alleles, while antibodies binding the epitope at 480-494 are found almost exclusively in the sera of patients with a Bg/II 9.8-kb polymorphism of the T cell receptor beta gene. Meanwhile, in these same patient sera the level of autoantibodies binding the complete 60-kD Ro particle is associated with a distinct pattern of alleles at these same immunoregulatory loci. These data demonstrate that component parts of autoantibody responses may be under genetic control which can be distinguished from the HLA associations characteristic of the response to the intact, complete autoantigen.