ALLOGENIC MHC CLASS-II DETERMINANT(S) IN MRL LPR AUTOIMMUNE DISEASE-PRONE MICE - UNUSUAL EXPRESSION OF AN L1 TRANSPOSABLE ELEMENT CREATES MOLECULAR MIMICRY

In some aged MRL/lpr autoimmune disease-prone mice, unexpected reactiv ity has been observed between lymphoid cells and mAb or polyclonal ant ibodies directed against the A(beta)d class II chain of the MHC. Howev er, Southern blot analysis of their genomic DNA, using different class I and class II MHC-specific probes, confirmed their inbred character and their H-2k genotype. In this study, inmmunoprecipitation experimen ts with an anti-A(beta)d mAb indicated that the 4-5 (and 12)-kD molecu le(s) recognized by an anti-A(beta)d mAb differed from a class II chai n. After specific antibody screening of a lambdagt11 expression librar y constructed with MRL/lpr ''A(beta)d-positive'' lymphoid cells, we cl oned cDNA that share sequences with high homology (>80%) to the 3' end of a 7-kb L1Md (L1) element propagated in the mouse genome via retrot ransposition. Northern blot analysis showed an overtranscription of th ese L1 sequences in the MRL/lpr spleen cells used for the construction of the cDNA library, in comparison to the MRL ancestor strains. There fore, the autoimmune MRL/lpr strain could express a translation produc t of L1 open reading frame 2, which mimics a ''highly antigenic'' epit ope of an allogenic MHC class II Ag.