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 reactivity has been observed between lymphoid cells and mAb or polyclonal antibodies directed against the A_β^d class II chain of the MHC. However, Southern blot analysis of their genomic DNA, using different class I and class II MHC-specific probes, confirmed their inbred character and their H-2^k genotype. In this study, immunoprecipitation experiments with an anti-A_β^d mAb indicated that the 45 (and 12)-kD molecule(s) recognized by an anti-A_β^d mAb differed from a class II chain. After specific antibody screening of a λgt11 expression library constructed with MRL/lpr "A_β^d-positive" lymphoid cells, we cloned 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 retrotransposition. Northern blot analysis showed an overtranscription of these L1 sequences in the MRL/lpr spleen cells used for the construction of the cDNA library, in comparison to the MRL ancestor strains. Therefore, the autoimmune MRL/lpr strain could express a translation product of L1 open reading frame 2, which mimics a "highly antigenic" epitope of an allogenic MHC class II Ag.