PATTERN OF ANTI-SMALL NUCLEAR RIBONUCLEOPROTEIN ANTIBODIES IN MRL MP-LPR/LPR MICE SUGGESTS THAT THE INTACT U1 SNRNP PARTICLE IS THEIR AUTOIMMUNOGENIC TARGET/

MRL/Mp-lpr/lpr (MRL/lpr) mice develop anti-Sm Abs that bind the B and D proteins of the U1 and other U small nuclear ribonucleoproteins (snR NPs). Humans with SLE also develop anti-Sm, but in contrast to MRL/lpr mice, anti-Sm Abs in humans are virtually always accompanied by anti- snRNP Abs that bind the A and 70 kDa proteins of the U1 snRNP. In this study, we identified anti-U1 snRNP Abs in 60% of MRL/lpr mice (40 of 66 animals), with the earliest and most frequent response directed aga inst the A protein. This response was either accompanied or closely fo llowed by Abs to other snRNP proteins, including the 70-kDa protein of the U1 particle and the B and D proteins that represent the anti-Sm r esponse. Other U snRNPs were rarely bound by these sera, analogous to previous observations in human SLE. Using in vitro translated 5' and 3 ' deletion mutants, we found that these early Abs principally bound an epitope on the COOH-terminal of the murine A protein. As shown previo usly, human sera with anti-ill snRNP reactivity bind a similar epitope . In summary, we have shown that anti-snRNP Abs in MRL/lpr mice are co mposed of a linked group of specificities against proteins of the U1 s nRNP particle, similar to human SLE, These observations, in conjunctio n with our previous findings that intact snRNPs are necessary for dive rsification of Abs in normal mice immunized with snRNPs, strongly sugg ests that intact U1 particles may be targets of the immune response in this disease.