RNA RECOGNITION BY AUTOANTIGENS AND AUTOANTIBODIES

The La, Ro, Sm and RNP autoantigens have been intensely studied over t he past decade since cDNAs encoding autoantigens have become available . Most of these autoantigens are closely associated with RNA in RNP pa rticles and molecular studies have provided insights into their modes of recognition and binding to RNA. For example, a common RNA Recogniti on Motif (RRM) was found to be a critical component of the RNA-binding domain of these autoantigens and the three dimensional structure of t he RRM has been solved. As described in other articles in this series, the presence of La, Ro, Sm and RNP autoantibodies correlates with dis ease subsets, such as Sjogren's syndrome, systemic lupus erythematosus and other connective tissue diseases. Immunological analysis of sera from autoimmune patients using recombinant autoantigens has revealed t hat multiple epitopes reside along the proteins and these represent bo th continuous and discontinuous (conformational) autotopes. Findings t o date support a model of autoantibody induction which involves the di rect presentation of proteinaceous autoantigens to the immune system. Circumstantial evidence has suggested that immunological crossreactivi ty between systemic autoantigens and structural components of infectio us agents may play an initial role in the autoimmune response to certa in antigens. However, the etiology of autoimmune diseases is probably multifactoral with genetic and other immune features acting on the org anismal level. In addition, RNA molecules themselves can be autoantige ns with higher order structural conformations which are recognized by RNP-type autoantibodies. Immune crossreactivity and/or direct presenta tion may generate autoantibodies reactive with conformational RNA epit opes. If crossreactivity with components of cellular or infectious age nts give rise to RNA epitopes, they may represent structural or functi onal mimetics of the primary epitopes that actually drive the response . These ideas are discussed with respect to the role of mimetic proces ses in molecular recognition during autoimmunity.